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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
3 mg/kg bw/day
Additional information

No treatment related effects were observed upon fertility in the key study, although there were some indications that treatment at 10 mg/kg/day resulted in lower number of pups born, fewer number of corpora lutea in the caesarean females, lower mean pup weights at weaning and lower mean foetal weight in the third generation. Based on observations and based on systemic toxicity in parent animals, the NOAEL of the study was set at 3 mg/kg/day.

In a supportive study investigating male fertility (Linder et al., 1982) treatment for 77 days at 150 ppm (9.1 mg/kg/day) had no effect on reproductive performance although causing sperm abnormalities and reduction in number, as well as minimal testicular changes, which were reversible within 16 weeks following treatment. In another supportive study (Spencer et al., 1982), disruption of the uterine environment (i.e. decrease in uterine protein and glycogen content) was demonstrated using decidualized pseudo-pregnant rats, with a NOEL established at 3.6 mg/kg/day.


Short description of key information:
The key study was conducted according to the OECD 416 guideline and was performed on the rat using dietary concentrations to give constant intakes of 0, 1, 3 & 10mg/kg bw/day. Animals were dosed continuously over 3 generations and effects on systemic toxicity, fertility and development were observed.
A yellowish tinge to the skin and reduced bodyweight gain were observed in the highest dose group, therefore the NOAEL was set at the mid dose level.

Effects on developmental toxicity

Description of key information
The key oral study was conducted according to the OECD 414 guideline and was performed on the rat using dosage levels of 0, 1, 3 & 10 mg/kg bw/day. The key dermal study was conducted according to US EPA guidelines (1986) and was performed on the rabbit using dosage levels of 0, 1, 3 and 9 mg/kg bw/day.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
3 mg/kg bw/day
Effect on developmental toxicity: via dermal route
Dose descriptor:
NOAEL
1 mg/kg bw/day
Additional information

No effects were observed upon teratogenicity in the key oral study. Retarded ossifications as well as reduced foetal body weights, noted at 10 mg/kg bw/day, were considered secondary to maternal toxicity. In a supportive study (McCormack et al. 1980), intraperitoneal injection of dinoseb at 8 mg/kg/day (non-lethal for the mothers) during the specific window days 10-12 of pregnancy caused dilated renal pelves and ureters in pups; these changes, however, were transient, and renal function was not affected in pups of 42 days of age. Another supportive study (Datson et al. 1988) also showed that these changes are temporary.

Giavini et al. (1986) showed that treatment by oral gavage resulted in no teratogenic effects, even at dosages markedly toxic for the mother (15 mg/kg/day), whereas dietary treatment at a slightly higher dose (200 ppm - 18-19 mg/kg/day) caused microphthalmia.

Specific teratogenic effects (anophthalmia and hydrocephaly) occurred also in the key dermal study, in the presence of maternal toxicity in does treated at 3 mg/kg bw/day, therefore the NOAEL was set as 1mg/kg/bw/day.

Justification for classification or non-classification

Dinoseb is included in Annex VI of EC Regulation 1272/2008 for reproductive and developmental effects. Based on possible treatment-related effects observed in the key, multi-generation study, the supportive studies investigating male and female fertility separately and on results of the dermal teratogenicity key study including the supportive oral study by Giavini et al. (1986), it is considered appropriate to classify the substance as listed on Annex VI of EC Regulation 1272/2008.