WHO cancer studies: Roundup – only 5 pesticide companies telling us ‘no-carcinogenicity’.

Total 5 unpublished, studies. No peer review, directly supplied and paid by:round hay bales France

  1.  Cheminova         Atkinson et al 1993a
  2.  Syngenta             Milburn 1996
  3.  Monsanto           Stout & Ruecker 1990
  4.  Cheminova         Atkinson 1993b
  5.  Syngenta             Brammer 2001

 

WHO/FAO toxicological evaluations become pesticide residue levels for countries that are part of Codex.  Most likely it is your country.

Background info: The Joint FAO/WHO Meeting on Pesticide Residues (JMPR) assesses pesticide residues. The JMPR does not represent governments.  JMPR, which consists of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group, has been meeting regularly since 1963.

Evaluations are found as Parts (I) Residues in Food and (II)Toxicological.

Page 158  “In the view of the absence of a carcinogenic potential in animals and the lack of genotoxicity in standard tests, the Meeting concluded that glyphosate is unlikely to pose a carcinogenic potential to humans.”

Glyphosates Codex Classification Number 158.

Pesticide Residues in food – 2004, Joint FAO WHO Meeting on Pesticide Residues

Evaluations 2004 – Part II  Toxicological   By IPCS  International Programme on Chemical Safety

 

Long-term studies of toxicity and carcinogenicity………………………. 121

(Please note these are extracts. The complete studies released to the public are available here.)

Mice  P.121

1. Atkinson, C., Martin, T., Hudson, P. & Robb, D. (1993a) Glyphosate: 104 week dietary carcinogenicity study in mice. Unpublished report No. 7793, IRI project No. 438618, dated 12 April 1991, from Inveresk Research International, Tranent, Scotland. Submitted to WHO by Cheminova A/S, Lemvig, Denmark.

In a study performed in compliance with the principles of GLP and according to the test guidelines of the US EPA and the OECD (TG 451), groups of 50 male and 50 female CD-1 mice were fed diets containing glyphosate (purity, 98.6%) at a concentration that  was adjusted weekly for the first 13 weeks and every 4 weeks thereafter to give doses of  0, 100, 300 and 1000mg/kg bw per day for 104 weeks.

The increased thymus weight in males at the intermediate and highest doses was not associated with any findings at necropsy or after histological evaluations.  Owing to the slight magnitude of the increase seen, the lack of a dose–response relationship, and the lack of an effect in females, the increases were considered to be chance effects.  During necropsy examinations, the incidence of lung masses was slightly higher in males at the highest dose (18/50) than in the control group (10/50); however, histopathology failed to reveal adverse lung findings. The occurrence of mineral deposits in the brain was significantly increased in males at the highest dose when compared with the control group (13/50 compared with 4/49). It should be noted that this is a common finding in mice of this age and strain.  There are no findings in the males and no findings at all in the females that could be attributed to treatment with glyphosate.

There were no statistically significant increases in the incidence of any tumours, either benign and malignant, in either sex when compared with the control groups. However, the number of animals with multiple types of tumour was slightly higher in both sexes at the highest dose (males, 16/50; females, 11/50) than in the controls (males, 11/50; females, 6/50). This led to a slight increase in the total number of tumours in the at the highest dose for both sexes (males, 60; females, 43) compared with the controls (males, 49; females, 36).  Haemangiosarcoma was evident in 4/50 males at the highest dose, in 2/50 females at the lowest dose, and in 1/50 females at the highest dose, but in none of the 50 animals of the control group. Histiocytic sarcoma in the lymphoreticular/ haemopoietic tissue was evident in 2/50 males at the lowest and highest doses, and in 3/50 females at the lowest and intermediate doses and 1/50 females at the highest dose when compared with the respective controls (0/50). Owing to the lack of a dose-response relationship, the lack of statistical significance and the fact that the incidences recorded in this study fell within the historical ranges for controls, these changes are not considered to be caused by administration of glyphosate.

In conclusion, administration of glyphosate to CD-1 mice for 104 weeks produced no signs of carcinogenic potential at any dose. The NOAEL was 1000mg/kg bw per day, the highest dose tested (Atkinson et al., 1993a).

Rats   Page 123

2. Milburn, G.M. (1996) Glyphosate acid: one year dietary toxicity study in rats. Unpublished report No CTL/P/5143, study no. PR1012, dated 2 October 1996, from Zeneca Agrochemicals, Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, England. Submitted to WHO by Syngenta Crop Protection AG, Basel, Switzerland.

In a study performed in compliance with the principles of GLP and according to the test guidelines of the US EPA and the OECD (TG 452), groups of 24 male and 24 female Alpk:APfSD (Wistar-derived) rats were given diets containing glyphosate (purity, 95.6%) at a concentration of 0, 2000, 8000 or 20000ppm for 1 year. Analysis of diets showed that the achieved concentrations, homogeneity and stability were satisfactory throughout the study. The calculated mean intakes were equal to 141, 560 and 1409mg/kg bw per day for males and 167, 671 and 1664mg/kg bw per day for females.

…..

Deviations in some clinical chemistry parameters, such as reductions in plasma concentration of cholesterol and triglycerides or a dose-related increase in plasma ALP activity throughout the study as well as occasional increases in the activities of plasma AST, ALT and creatine kinase, were mostly confined to groups receiving the high and intermediate doses and were probably treatment related.  In the absence of any histopathological findings, these changes are considered to be of marginal toxicological relevance.  There was no evidence of any effect of glyphosate on urine parameters.

At necropsy, there were no gross pathological findings that could be attributed to treatment and no consistent organ weight changes. Histopathology revealed an increased incidence and severity of focal basophilia of the acinar cells of the parotid salivary gland in both sexes at 20,000ppm. At 8,000ppm, this finding was of minimal severity and its incidence was only slightly above that in the control animals.  No other microscopic findings could be ascribed to administration of glyphosate.

Similar numbers and types of neoplasms were diagnosed in the control group and in the group receiving glyphosate at 20000ppm, but the duration of the study was not sufficiently long to enable final conclusions to be made with regard to carcinogenicity. The NOAEL was 2000ppm, equal to 141mg/kg bw per day, on the basis of a reduction in body weight and clinical chemistry findings at dietary concentrations of 8000ppm and greater (Milburn, 1996).

Page 124

3. Stout, L.; Ruecker, F. (1990) Chronic Study of Glyphosate Administered in Feed to Albino Rats: Lab Project Number: MSL- 10495: R.D. 1014. Unpublished study prepared by Monsanto Agricultural Co. 2175 p.    MRID 41643801

In a study performed in compliance with the principles of GLP and according to the test guidelines of the US EPA, groups of 60 male and 60 female Charles River CD®(SD)BR rats were fed diets containing glyphosate (purity, 96.5%) at a concentration of 0, 2000, 8000 or 20000ppm for 2 years. The calculated mean intakes were equal to 89, 362 and 940mg/kg bw per day in males and 113, 457 and 1183mg/kg bw per day in females.

…..

There were no statistically significant differences in mortality during the study.  No evidence of treatment-related clinical signs was recorded except the opthalmological findings mentioned below. Statistically significant reductions in body weight were noted in females at the highest dose from week 7 to approximately month 20. During this time absolute body weights gradually decreased to 14% below the control value owing to a reduction in body-weight gain by up to 23%. In contrast, body-weight gain in all treated male groups was comparable to that of the controls.  Food consumption was not adversely affected by treatment in any sex despite an increase in males at the highest dose.

The opthalmic examination before study termination revealed a statistically significant difference (p < 0.05) between the incidences of cataractous lens changes in males in the control group and in the group receiving the highest dose (none out of 15 compared with five out of 20). The occurrence of cataractous lens changes in males at the lowest and intermediate doses, as well as in all treated groups of females, were comparable to that of their respective controls. The observed incidence for this finding of 25% for male CD rats at the highest dose was within the range (0–33%) observed in previously conducted studies at this laboratory, but a treatment-related impact could not be excluded. An independent pathologist’s examination confirmed a statistically significant increase (p<0.05) in the incidence of cataractous lens changes in males at the highest dose (one out of 14 compared to 8 out of 19) and concluded that there appeared to be a treatment related occurrence of lens changes affecting males at the highest dose. Histological examination of the eyes at study termination revealed the incidences of cataract and/or lens fibre degeneration. The results of histopathology also suggested that there was an increase in cataractous lesions in male rats at 20,000ppm, although the difference in incidences in the control group and at the lowest and intermediate doses was less pronounced than suggested by ophthalmoscopy.

This outcome was essentially confirmed by re-evaluation by an independent laboratory.  It concluded there was a slight, statistically significant (as indicated in the Cochrane-Armitage linear trend test) increased incidence of basophilic degeneration of the posterior subcapsular lens fibres in males at the highest dose, but not in those at the intermediate or lowest dose, nor in any treated group of females.

There were various changes in haematology and serum chemistry parameters, but these changes were not consistently noted at more than one time-point, were within ranges for historical controls, were small in magnitude, and/or did not occur in a dose-related manner. Therefore, they were considered to be either unrelated to treatment or toxicologically not significant. However, the statistically significant increase in alkaline phosphatase activity in females at the highest dose at study termination is in line with observations made in other long term studies in rats, although it was partly attributable to one animal with an outstandingly high value. Statistically significant reductions in urine pH were noted in males at the highest dose at monthe 6,18 and 24, reflecting the renal excretion of glyphosate, which is an acid.

Statistically significant increases in liver weight were noted in males at the highest dose. There were no other statistically significant changes in organ weights that occurred in a dose-related manner. Gross abnormalities observed at necropsy were not considered to be related to administration of glyphosate.

Regarding neoplastic lesions, the only statistically significant difference between the control and treated animals was an increase in the incidence of pancreatic islet cell adenomas in males at the lowest dose. The incidences of this lesion were 1/58 (2%), 8/57 (14%), 5/60 (8%), and 7/59 (12%) in males in the control group and at the lowest, intermediate and highest dose, respectively. The historical-control range for this tumour at the testing laboratory was 1.8–8.5%, but a partial review of studies reported recently in the literature revealed a prevalence of 0–17% in control males with several values being ≥ 8%. More importantly, the incidences of islet cell adenomas clearly did not follow a dose-related trend in the treated groups of males, as indicated by the lack of statistical significance in the Pedro trend test. It should be noted that there was also considerable intergroup variability in the numbers of females with this tumour (5/60, 1/60,4/60,0/59 in the control group and at the lowest, intermediate and highest group respectively). There was no evidence of dose-related pancreatic damage or pre-neoplastic lesions. Taken together, the data support the conclusion that the occurrence of pancreatic islet cell adenomas in male rats was spontaneous in origin and unrelated to administration of glyphosate.

With regard to non-neo-pastic (changes (apart from the findings in the eye, described above), histopathological examination revealed an increase in the number of animals displaying inflammation of the stomach squamous mucosa at 8000 and 20,000ppm, achieving statistical significance for females only at the intermediate dose.

Although the incidence of this lesion in females at the intermediate dose (15%) was slightly outside the range for historical controls (0–13.3%) for the laboratory, there was no dose-related trend across all groups of treated females and there was no significant difference in any group of males.  Therefore, it is equivocal whether this finding was treatment-related.  However, a weak irritation potential of the test material may be assumed at high doses. In contrast to other long-term studies, no histological changes in salivary glands were reported. However, it must be mentioned that in this study only the mandibular (submaxillary) salivary glands were evaluated microscopically, and not the parotid glands.

In conclusion, administration of glyphosate to Sprague-Dawley rats for 24 months produced no signs of carcinogenic potential. The NOAEL was 8000ppm, equal to 362mg/kg bw per day, on the basis of a reduction in body weight in females and cataractous lens changes in males at 20000ppm (Stout & Ruecker, 1990)

 

P.127.

4. Atkinson, C., Strutt, A.V., Henderson, W., Finch, J. & Hudson, P. (1993b) Glyphosate: 104 week combined chronic feeding/oncogenicity study in rats with 52 week interim kill (results after 104 weeks.). Unpublished report No. 7867, IRI project No. 438623, dated 7 April 1993, from Inveresk Research International, Tranent, Scotland. Submitted to WHO by Cheminova A/S, Lemvig, Denmark.

In a study performed in compliance with the principles of GLP and according to the test guidelines of the US EPA, groups of 85 male and 85 female Sprague-Dawley rats were fed diets containing glyphosate (purity, 98.7–98.9%) at a concentration that was adjusted weekly for the first 12 weeks and every 2 months thereafter to give doses of 0, 100, 300 and 1000mg/kg bw per day for 104 weeks.

I have placed this important study (Atkinson 1993b) separately here as this study establishes the NOAEL of 100mg/kg bw/day which becomes the ADI for the WHO/FAO. http://www.safesayswho.com/?p=484

P.129.

5. Brammer, A. (2001) Glyphosate acid: two year dietary toxicity and oncogenicity study in rats. Unpublished report No. CTL/PR1111, study No. PR1111, dated 15 March 2001, from Zeneca Agrochemicals, Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, England. Submitted to WHO by Syngenta Crop Protection AG, Basel, Switzerland

In a study performed in compliance with the principles of GLP and according to the test guidelines of the US EPA and the OECD (TG 453), groups of 52 male and 52 female Alpk:APfSD (Wistar-derived) rats were fed diets containing glyphosate (purity, 97.6%) at a concentration of 0, 2000, 6000 or 20000ppm for 2 years. A further 12 males and 12 females were added to each group and were designated for interim kill after 1 year. The calculated mean intakes were equal to 121, 361 and 1214mg/kg bw per day in males and 145, 437 and 1498mg/kg bw per day in females.

….

Minor variations from mean values for the controls were obtained for most haematological paramaters, but showed no consistency and were confined to intermediate time-points and/or doses and these changes were thus considered not to be treatment related. In contrast, some clinical chemistry findings were assumed to be caused by administration of glyphosate, at least at the highest and intermediate doses. There was a clear dose-related increase in plasma ALP activity in both sexes throughout the study reaching statistical significance at the two higher doses. In the groups at 2000ppm, the mean values also tended to be higher, however this increase was marginal and only occasionally achieved statistical significance (in males at week 79 and females at week 53). In addition, there was evidence of increases in plasma ALT and AST activities, and in total bilirubin concentration at one or more time-points. These findings were confined to the groups receiving the intermediate and highest doses and frequently occurred in one sex only.  In males at the highest dose, plasma concentrations of triglycerides and cholesterol were consistently decreased throughout the study. Plasma concentrations of creatinine were lower in all treated female groups at week 27 and in females receiving 6000 and 20000ppm at week 14, but in the absence of any effects later in the study, this was considered as having occurred by chance rather than suggesting an adverse effect. In males at the highest dose of 20,000ppm, urinary pH was lower than in controls throughout the study, and the incidence and number of erythrocytes in the urine was increased in males and, to a lesser extent, in females.

No increase in tumour incidence was observed. A number of probably treatment related macroscopic findings were seen in males at 6000ppm and/or 20000ppm, consisting of a minor increase in the incidence of enlarged kidneys, single masses in the liver, firmness of the prostate and a reduction in the incidence of reduced testes. However, there were no consistent, dose-related and/or statistical significant organ-weight changes that could be considered to indicate an adverse effect of glyphosate.

In contrast to the previous 1-year feeding study in rats (Milburn, 1996, see above) that was performed in the same laboratory and on the same rat strain, microscopic changes were seen in the liver and kidneys, but not the salivary glands of rats at 20000ppm (Table24). Changes in the liver comprised a weak and rather equivocal increase in the incidence of hepatitis (evidence obtained in male only) and proliferative cholangitis, but the severity of the latter finding was not altered. There were a number of changes in the kidneys of both sexes, notably renal papillary necrosis, with or without papillary mineralisation, and transitional cell hyperplasia. The incidence was greater in males than females. These renal findings were considered to be related to treatment but are consistent with the feeding of very high doses of an acidic material, which may also have caused the microscopically observed prostatitis and periodontal inflammation observed. A decrease in the incidence of tubular degeneration of the testis in males at 20,000 ppm was considered to be without adverse consequence.

In conclusion, dietary administration of glyphosate at up to the highest dietary concentration of 20000ppm for up to 2 years produced little evidence of toxicity in the  long term, with the kidney, the prostate and possibly the liver being the target organs. A number of findings (eg. Renal papillary necrosis, prostatitis, periodontal inflammation and urinary acidosis) might be attributed to the acidity of the test substance. No indications of neurotoxicity were obtained. The improved survival in males at the highest dose was likely to be associated with lower food consumption, lower body weights and a decreased severity of renal glomerular nephropathy. In the absence of treatment-related histopathalogical findings at 2000 and 6000ppm, the marginal changes in some clinical chemistry parameters at these doses were considered to be of no toxicological significance.

Administration of glyphosate for 2 years produced no evidence of a carcinogenic response to treatment in rats. The NOAEL was 6000ppm (equal to 361mg/kg bw per day), on the basis of a reduction in body weight and food consumption, and indications for kidney, prostate and liver toxicity at 20000ppm (Brammer, 2001).

 

To see the US EPA studies. Or the information behind the EPA Carcinogenicity assessments. Note the Monsanto Stout & Ruecker study is also used.  The pool of actual studies used to declare carcinogenicity for the USA & WHO is very small.

and of course, studies never use the complete Roundup formulation – only the weaker active chemical glyphosate.

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