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Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
In an OECD 422 study on the substance (Males: 39d; Females: 49/53d) and an OECD 421 on its methyl analogue (1561-92-8) (Males: 29d; Females: 41/46d) the NOAEL was 1000 mg/kg/d demonstrating comparable sub-chronic toxicity between the 2 substances.

Based on this, the sub-chronic (90d) NOAEL can be based on the results of the OECD 408 performed on the same analogue of 500 mg/kg/day.

Since the only use of the substance (and only exposure) will be as an intermediate (monomer) in polymerization, where the exposure level in the workplacewill be significantly below the DNEL, use of the analogue data avoids unnecessary animal testing and fufills the criteria of Annex XI.
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The DNEL for long-term exposure by the inhalation route was derived using route-to-route extrapolation from the NOAEL obtained in a repeated dose (90-day) oral toxicity study in rats on the methyl analogue of the substance:Sodium 2-methylprop-2-ene-1-sulphonate(216-341-5 /1561-92-8). No adverse effects were observed at the dose of 500 mg/kg bw/d.

This value which was taken as relevant dose descriptor for long-term toxicity was modified in order to get the correct starting point for DNEL derivation.

In a GLP study according to OECD guideline 422, the test item was given daily as an aqueous solution to groups of 10 male and 10 female Wistar rats (F0 animals) by gavage at doses of 100, 300 and 1000 mg/kg body weight/day (mg/kg bw/d) (BASF SE, 2010f). Control animals (10 male and 10 female Wistar rats) were dosed daily with the vehicle only (drinking water). The duration of treatment covered a 2-week pre-mating and a mating period in both sexes, approximately 1 week post-mating for males, and the entire gestation period as well as 4 days of lactation and approximately 1 week thereafter for females.The female animals were sacrificed 49 or 53 days after the beginning of the administration, and examined. The male animals were sacrificed 35 days after the beginning of the administration, and examined.

After 2 weeks of premating treatment the F0 animals were mated to produce F1 generation pups. Mating pairs were from the same test group. Mating was discontinued as soon as sperm was detected in the vaginal smear. F0 animals were examined for their reproductive performance including determination of the number of implantation sites and the calculation of postimplantation loss for all F0 females. A detailed clinical observation was performed in all animals before initial test substance administration and, as a rule, thereafter at weekly intervals. Food consumption of the F0 parents was determined once weekly during premating. In dams food consumption was determined for gestation days 0 - 7, 7 - 14, 14 - 20 and lactation days 1 - 4. Body weights of F0 parents were determined once a week, in males throughout the study and in females during premating. During gestation and lactation period, F0 females were weighed on gestation days (GD) 0, 7, 14 and 20, on the day of parturition (postnatal day [PND] 0) and on PND 4. The pups were sexed and examined for macroscopically evident changes on PND 0. They were weighed on PND 1 and on PND 4. Their viability was recorded. At necropsy on PND 4, all pups were sacrificed with CO2, under isoflurane anesthesia, and examined macroscopically for external and visceral findings.

 

Clinicochemical and hematological examinations as well as urinalysis were performed in 5 parental animals of either sex towards the end of the administration period. At the end of the administration period a functional observational battery was performed and motor activity was measured in 5 parental males and females per group. All F0 parental animals were sacrificed by decapitation,under isoflurane anesthesia, and were assessed by gross pathology. Weights of selected organs were recorded and a histopathological examination was performed.

 

The various analytical analyses confirmed compound identity using IR- UV- and NMR-spectroscopic methods, demonstrated the stability of the test substance solutions in drinking water at room temperature for a period of 7 days and confirmed the overall accuracy of the prepared concentrations.

The following test substance-related adverse effects/findings were noted:

 

Test group 3 (1000mg/kg bw/d)

F0/ Parental animals: No test substance-related adverse findings

 

Test group 2 (300 mg/kg bw/d)

F0/ Parental animals: No test substance-related adverse findings

 

Test group 1 (100 mg/kg bw/d)

F0/ Parental animals: No test substance-related adverse findings

 

Conclusion

Under the conditions of this Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test in Wistar Rats Golpanol ALS wasserfrei had no adverse effects on fertility of the F0 parental animals of both sexes at 100; 300 and 1000 mg/kg bw/d.

 

The test substance caused also no impairments of the reproductive performance. Mating behaviour, conception, gestation, parturition, as well as sexual organ weights and gross and histopathological findings of these organs were not influenced up to 1000 mg/kg bw/d.

 

No general systemic toxicity was noted in the F0 parental animals at all dose levels tested. Golpanol ALS wasserfrei caused no indicationsof test substance-induced effects in low-, mid- and high-dose rats regarding considering food consumption and body weights/ body weight gain as well asdetailed clinical examinations in an open field, in a functional observational battery (FOB) and measurements of motor activity.

 

Concerning clinical and gross pathology as well as histopathology all findingsoccurred either singly or were biologically equally distributed over the control group and the treatment groups. They are considered to be incidental or spontaneous in origin and without any relation to treatmentup to 1000 mg/kg bw/d.

 

Up to 1000 mg/kg bw/dGolpanol ALS wasserfrei caused no developmental toxicity. No alteration of the pre-/postnatal development of the F1 offspring was indicated in number of delivered, liveborn and stillborn pups as well as survival, weight/weight gain, and sex ratio of pups.

 

Thus, under the conditions of the screening test the NOAEL (no observed adverse effect level) for general, systemic toxicity was ≥ 1000 mg/kg bw/d for the F0 parental rats, the highest dose tested.

 

In an OECD 421 performed on the methyl analogue (1561-92-8) (Males: 29d; Females: 41/46d) the NOAEL was 1000 mg/kg/d demonstrating comparable sub-chronic toxicity between the 2 substances. Based on this, the sub-chronic (90d) NOAEL can be based on the results of the OECD 408 performed on the analogue of 500 mg/kg/day.

Justification for classification or non-classification

No substance-related effects were observed in a screening test for reprotoxic effects in rats in doses up to 1000 mg/kg bw/d. Therefore, no indication is given for classification according to the criteria of DSD (67/548/EEC) and CLP (1272/2008/EC), respectively. Furthermore, the NOEAL in the methyl analogue (1561 -92 -8) is 500 mg/kg/day.