P-1401

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Data waiving (study scientifically not necessary / other information available): A screening reproduction / developmental study does not need to be conducted because a pre-natal developmental toxicity study is available.

Data waiving (study scientifically not necessary / other information available): In accordance with column 1 of REACH Annex IX, a two-generation reproductive toxicity study does not need to be conducted since the repeated dose toxicity study does not indicate adverse effects on reproductive organs or tissues.

Link to relevant study records

Reference

Reference 1

Endpoint:

screening for reproductive / developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because a pre-natal developmental toxicity study is available

Reason / purpose for cross-reference:

data waiving: supporting information

Reproductive effects observed:

not specified

Reference 2

Endpoint:

extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Data waiving (study scientifically not necessary / other information available): A screening reproduction / developmental study does not need to be conducted because a pre-natal developmental toxicity study is available.

Data waiving (study scientifically not necessary / other information available): In accordance with column 1 of REACH Annex IX, a two-generation reproductive toxicity study does not need to be conducted since the repeated dose toxicity study does not indicate adverse effects on reproductive organs or tissues.

Effects on developmental toxicity

Description of key information

Key study: Read-across from experimental data on an analogue. Test method OECD Guideline 414. GLP study. The NOEL for both maternal and developmental toxicity by oral route in rats was determined to be 1000 mg/kg/day since no effects were observed at the highest dose tested.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across from an analogue substance for which a guideline study (Klimish 1) is available.

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Read-across approach from data on an analogue substance.

Limit test:

no

Key result

Dose descriptor:

NOEL

Remarks:

Maternal toxicity

Effect level:

1 000 mg/kg bw (total dose)

Based on:

test mat.

Basis for effect level:

other: No adverse effects observed at any dose tested.

Remarks on result:

other: Based on a read across from an analogue substance.

Key result

Abnormalities:

no effects observed

Key result

Dose descriptor:

NOEL

Remarks:

Developmental toxicity

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed at any dose tested.

Remarks on result:

other: Based on a read-across from an analogue substance.

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

Conclusions:

Based on the read-across approach, the NOEL for pre-natal developmental toxity by oral route in rats was determined to be 1000 mg/kg bw/day.

Executive summary:

Based on experimental results obtained in a study according to OECD 414 on the analogue substance FB220 where the test item did not produce developmental and/or maternal toxicity, the read-across approach is applied and the NOEL for pre-natal developmental toxity by oral route in rats for the subtance P-1401 was determined to be 1000 mg/kg bw/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The study is GLP compliant and of high quality (Klimisch score = 1). Since read-across approach was applied the Klimisch score is = 2.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Key study: Read-across approach from experimental data on the analogue substance CAS 16470-24-9:

A pre-natal developmental toxicity test was performed on the analogue substance CAS 16470-24-9 according to OPPTS Guideline 870.3700, equivalent to OECD Guideline 414 (GLP study). Dose levels up to1000 mg/kg/day were administered via oral gavage daily from Days 6 through 19 of gestation at a volume of 10 mL/kg. The females were time mated upon delivery. Litters were delivered by cesarean section an Day 20 of gestation. All findings were either comparable with the concurrent vehicle control and/or historical control incidences. The No Observed Effect Level (NOEL) for both maternal and developmental toxicity was 1000 mg/kg/day. The substance was determined to be not teratogenic in rats following oral administration of dose up to and including 1000 mg/kg-bw/day.

Justification for classification or non-classification

Based on available data, the substance is not classified for developmental toxicity according to CLP Regulation (EC) No. 1272/2008.