| Study author and date |
Submitter company |
Experimental animal/exposure route |
Doses used
mg/kg bw/d |
Effects found |
Dose-related effects/Statistical significance |
| Suresh, 1993 |
Feinchemie |
Rabbits/gavage |
0, 20, 100, 500 |
Dilated heart |
Linear dose-response relationship. Significantly elevated at all doses, including low dose |
| |
|
|
|
Unspecified “major visceral malformations” |
Linear dose-response relationship. Increased in all treatment groups, significantly increased at highest dose |
| |
|
|
|
Extra 13th rib |
Linear dose-response relationship. Statistically significant increase at highest dose |
| Brooker et al., 1991 |
Monsanto/Cheminova |
Rabbits/gavage |
0, 50, 150, 450 |
Heart malformations (only type specified is interventricular septal defect) |
Effect found at highest dose. No information provided by Germany on statistical significance |
| |
|
|
|
Embryonic deaths |
Significant at all doses, though no clear dose/response relationship |
| Bhide and Patil, 1989 |
Barclay/Luxan |
Rabbits/route unstated |
0, 125, 250, 500 |
Heart malformation (ventricular septal defect) |
Linear dose-response relationship. No statistical analysis provided by authors. Increased heart malformations found in all treatment groups |
| |
|
|
|
Lungs: postcaval lobe absent |
Linear dose-response relationship. No statistical analysis provided by authors. Dose-dependent increases found in all treatment groups |
| |
|
|
|
Kidneys absent |
Linear dose-response relationship. No statistical analysis provided by authors. Dose-dependent increases found in all treatment groups |
| |
|
|
|
Rudimentary 14th rib, unilateral |
No statistical analysis provided by authors. Dose-dependent increases found in mid- and high-dose groups |
| |
|
|
|
Number of viable foetuses per litter decreased and number of non-viable implants increased |
Linear dose-response relationship in case of non-viable implants. No statistical analysis provided by authors. Effects found at high dose level. |
| Tasker et al., 1980 |
Monsanto/Cheminova |
Rabbits/gavage |
0, 75, 175, 350 |
Increased number of deaths in dams |
Linear dose-response relationship. 1, 2, and 10 deaths in low, mid- and high-dose treatment groups respectively (no. of rabbits per group: 16 or 17). 75 mg/kg stated by Germany to be NOAEL |
| Anon., 1981 |
Alkaloida |
Rats and rabbits/oral feeding |
0, 10.5, 50.7, 255.3 |
Increased number of foetal deaths |
Effect seen at two upper dose levels |
| Zhu et al., 1984 |
Barclay |
Mice/gavage |
80, 420, 1050 |
Germany comments that there is “No evidence of dose-related toxic effects” and “no … structural malformations” but that description of experiment was “poor” |
Data not provided by Germany |
| Brooker et al., 1991 |
Monsanto/Cheminova |
Rats/gavage |
0, 300, 1000, 3500 |
Distortions affecting thoracic ribs |
Dose-dependent increases found in mid- and high-dose groups. Statistically significant at high dose |
| |
|
|
|
Reduced ossification of one or more cranial centres |
Dose-dependent increases found in mid- and high-dose groups. |
| |
|
|
|
Reduced ossification of sacro-caudal vertebral arches |
Dose-dependent increases found in mid- and high-dose groups |
| |
|
|
|
Unossified sternebrae |
Increases found in all treated groups, statistically significant at high dose |
| |
|
|
|
Skeletal variations |
Dose-dependent increases found in all treated groups, statistically significant in mid-dose and high-dose groups. |
| Tasker and Rodwell, 1980 |
Monsanto/Cheminova |
Rats/gavage |
0, 300, 1000, 3500 |
Unossified sternebrae |
Increase found at highest dose level |
| |
|
|
|
Unspecified malformations |
Increase at highest dose level |
| |
|
|
|
No. of viable foetuses per litter and mean foetal weight decreased |
Effects found at highest dose level |
| |
|
|
|
Early resorption of embryos |
Data not provided by Germany |
| Suresh, 1991 |
Feinchemie |
Rats/gavage |
0, 1000 |
Increase in delayed ossification (caudal vertebral arch, forelimb proximal and hindlimb distal phalanges) found in treatment group, but increase in delayed ossification of skull found in control group |
Conflicting data led Germany to conclude that the NOAEL for developmental toxicity was 1000 mg/kg |
| Bhide, 1986 |
Barclay/Luxan |
Rats/gavage |
0, 100, 500 |
No effects found but Germany commented that “serious reporting deficiencies” and lack of statistical analysis led it to consider the study as supplementary information only |
In spite of lack of reliable data, Germany derived a NOAEL for developmental toxicity of 500 mg/kg |
| Anon., 1981 |
Alkaloida |
Rats and rabbits/oral feeding |
22, 103, 544 |
Germany commented that description of study is so “poor” that it only considered the study as supplementary information. There were “no malformations recorded” and effects on foetuses were “not observed” but it is unclear from Germany’s summary whether this was due to poor reporting by the study’s authors or if there was an actual absence of effects |
In spite of lack of reliable data, Germany derived a NOAEL for developmental toxicity of 544 mg/kg |
