2-hydroxy-4-(trifluoromethyl)benzoic acid

Toxicity to reproduction

Administrative data

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

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to column 2 of REACH Annex VIII, the study does not need to be conducted if a pre-natal developmental study is available.

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH (see 'Attached justification')

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The analogue substance shares the same functional groups with the target and has a similar molecular weight, and comparable values for the relevant molecular properties.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
- Source: Triflusal.
- Target: TFMSA, see 'test item'.

3. ANALOGUE APPROACH JUSTIFICATION
Please find Reporting Format in 'Attached justification'.

4. DATA MATRIX
Please find Data Matrix included in 'Attached justification'.

Reason / purpose for cross-reference:

read-across source

GLP compliance:

not specified

Limit test:

no

Key result

Dose descriptor:

NOAEL

Effect level:

>= 24.9 - < 49.8 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

gross pathology

Remarks on result:

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

Key result

Abnormalities:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

49.8 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no significant effects were observed.

Remarks on result:

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

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

The results of the read-across approach from the experimental data obtained for the supporting substance are expressed as the estimated toxicity based on molecular weights. No other adaptation is necessary.

Conclusions:

Based on the available data for the read-across approach, the target substance has a NOAEL (maternal toxicity) ≥ 24.9 mg/kg bw/day and a NOAEL (developmental) ≥ 49.8 mg/kg bw/day in rabbits.

Executive summary:

Read-across from supporting substance (structural analogue or surrogate): A prenatal developmental toxicity test was conducted for the analogue substance Triflusal, according to OECD 414, under GLP contidions. The test item was administered daily by oral gavage to 16 pregnant female chinchilla rabbits per group at doses of 0 (vehicle control), 15, 30, or 60 mg/kg bw/day in bi-distilled water with 4% CMC from the 6th day to the 18th of pregnancy. The animls were observed daily for sings of toxicity from day 0 to day 28th of gestation, when they were sacrificed and the fetuses were removed from the uterus, weighed individually, examined for gross external abnormalities, sacrificed, and prepared for internal examination. This included external, visceral and skeletal examinations. Gross macroscopic examination of maternal animals was performed on all internal organs, with emphasis on the uterus, uterine contents, position of fetuses in the uterus and number of corpora lutea. Regarding maternal toxicity, the administration of the test item was associated with the death of 2 animals, body weight loss on the initiation of dosing and an increased incidence of macroscopic changes indicative of gastric irritation at 60 mg/kg bw/day and with reduced food consumption during the first 5 days of dosing at 30 and 60 mg/kg bw/day. Regarding developmental toxicity, there was no indication of an adverse effect of treatment with the test item on any of the maternal reproduction parameters or any of the fetal parameters up to and including the highest dose examined. For the analogue substance, the NOAEL (developmental) in rabbits was determined to be greater than 60 mg/kg bw/day; whereas the NOAEL (maternal toxicity) was found to be between 30 and 60 mg/kg bw/day. Based on the available data for the read-across approach, the target substance has a NOAEL (maternal toxicity) ≥ 24.9 mg/kg bw/day and a NOAEL (developmental) ≥ 49.8 mg/kg bw/day in rabbits.