Registration Dossier

Administrative data

Description of key information

No mortality or toxicity was observed in 2 reliable oral limit tests with doses of 5000 mg/kg bw.
A reliable acute dermal toxicity study is lacking, however, a WOE is used based on the following data:
• a LD50 value of > 5000 mg/kg bw from a less reliable study
• No observed acute oral toxicity up to doses of 5000 mg/kg bw in reliable studies
• Very low absorption at dermal exposure, based on an in vitro skin penetration study (see chapter 7.1.2), and
• No systemic effects after dermal exposure in a Local Lymph Node Assay (NOAEL >/= 863 µg/kg bw/day).
Based on this data, no acute dermal toxicity is expected within the range of classification limits.
Inhalation exposure is not an exposure route of concern.
Due to the organophosphorous structure or the submission substance, tests were performed with respect to an inhibition of cholinesterase. A reliable and a less reliable in vitro study revealed no anticholinesterase activity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Based on reliable studies the LD50 was > 5000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
There is no concern with respect to toxicity after acute dermal exposure: a less reliable study with a LD50 > 5000 mg/kg bw is supported by the lack of systemic toxicity in a reliable LLNA (NOAEL >/= 863 µg/kg bw/day for a threefold exposure), route-to-route considerations on toxicokinetics and reliable studies on oral acute toxicity studies with LD50 values > 5000 mg/Kg bw
Furthermore, an available fully reliable in vitro dermal penetration study demonstrates that the dermal penetatration of considerable amount of tne substance via skin can be excluded.

Additional information

Oral exposure

Rats were gavaged in two reliable limit tests (RL2) with 5000 mg/kg bw of the test substance each (“dispersion” or “active substance” were tested). No mortality or gross pathological alterations were reported. Therefore under the conditions of this study the LD50 for both test items is > 5000 mg/kg bw.

 

Inhalation exposure

This information is not available. In accordance with column 2 of section 8.5 of REACH Annex VIII, an acute inhalation toxicity study is not necessary because exposure of humans via inhalation is considered unlikely taking into account the vapour pressure of the substance and the physical form of the substances.

 

Dermal exposure

A LD50 value for dermal exposure of > 5000 mg/kg can be derived from a less reliable study (RL3). No reliable studies are available.

However, due to the following reasons there is no concern with respect to toxicity after acute dermal exposure:

- acute oral toxicity was not observed in reliable studies (RL2) and LD50 values are > 5000 mg/kg bw.

- dermal absorption is very low (0.02-0.05 %), based on a reliable in vitro skin penetration study (RL1, chapter 7.1.2). Even assuming the worst case of a higher toxicity via the dermal route, this would result in an estimated LD50 far above the classification limit.

- Supporting information comes from a LLNA, where no signs of toxicity were observed after three exposures up to 863 µg/kg bw/day(guideline study, but only RL3 with respect to acute dermal toxicity).

Based on this data, no acute dermal toxicity is expected within the range of classification limits. Inhibition of cholinesterase Due to the organophosphorous structure or the submission substance, tests were performed with respect to an inhibition of cholinesterase. A reliable (RL2) and a less reliable in vitro study (RL3) revealed no anticholinesterase activity.

Justification for selection of acute toxicity – oral endpoint
Two studies of identical quality with two different test items of the same submission substance are available

Justification for classification or non-classification

Based on the available data and considerations on acute dermal toxicity, the test substance has not to be classified for acute toxicity according to Regulation (EC) No 1272/2008.