Registration Dossier

Diss Factsheets

Administrative data

Description of key information

NOAEL test item (repeated oral toxicity male and female rats treated at least for 29 days) = 800 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
800 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Study conducted according to internationally accepted testing guidelines.

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

A Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test according to OECD TG 422 was performed on "Reaction mass of dodecane-1-thiol and tridodecyl trithiophosphite" . The test item was administered by oral gavage to Sprague Dawley rats (10 males and 10 females for each main group) using corn oil for vehicle at dose levels of 0, 50, 200 e 800 mg/kg bw/day. The assessment of delayed toxicity or persistence of adverse effects was performed on recovery groups (5 males and 5 females for each dose group) . Males of the main groups were treated for 2 weeks prior to pairing and during pairing with females until the day before necropsy, for a total of 29/30 days. Females were treated for 2 weeks prior to pairing, and thereafter during pairing, post coitum and postpartum periods until Day 13 post partum (for at least 51 days). Recovery animals (males) were treated for up to 4 consecutive weeks and killed after 4 weeks of recovery period. Recovery animals (females) were treated for up to 6 weeks and killed after 4 weeks of recovery period.

Nor mortality neither effects treatment related (i.e. difference in body weight, clinical signs including neurotoxicological evaluation, effects on haematology or clinical chemistry parameters, anomalies during the gross pathology investigation or during histophatological examinations) were observed both for main groups and for recovery groups (when examination was considered necessary) respect to control group. Based on the results of this study, the NOAEL (No Observed Adverse Effect Level) for repeated toxicity was considered to be 800 mg/kg bw/day for both males and females.

Justification for classification or non-classification

According to the CLP Regulation (EC n.1272/2008), classification in category 1 for repeated dose toxicity applies to substances that have produced significant toxicity in humans or that, on the basis of evidence from studies in experimental animals, can be presumed to have the potential to produce significant toxicity in humans following repeated exposure. Substances are classified in category 1 for target organ toxicity (repeat exposure) on the basis of:

— reliable and good quality evidence from human cases or epidemiological studies; or

— observations from appropriate studies in experimental animals in which significant and/or severe toxic effects, of relevance to human health, were produced at generally low exposure concentrations.

As for classification in category 2, it applies to substances that, on the basis of evidence from studies in experimental animals can be presumed to have the potential to be harmful to human health following repeated exposure. Substances are classified in category 2 for target organ toxicity (repeat exposure) on the basis of observations from appropriate studies in experimental animals in which significant toxic effects, of relevance to human health, were produced at generally moderate exposure concentrations.

 

For studies of 28 -day duration, classification in category 1 applies when toxicity by oral route is seen at concentrations below 30 mg/kg bw/day, while category 2 applies for toxicity at doses between 30 and 300 mg/kg bw/day.

 

Based on the results related to repeated toxicity obtained by Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test according to OECD 422 on the test item (i.e. NOAEL oral repeated toxicity male/female rats treated at least 29 days = 800 mg/kg bw/day), no classification after repeated exposure by oral route is suggested for " Reaction mass of dodecane-1-thiol and tridodecyl trithiophosphite" according to the CLP Regulation (EC n.1272/2008).

Categories Display