Phosphoric acid, butyl ester, sodium salt

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Adverse effects regarding development were observed with the read across-substance (CAS 107-66-4) at 1000 mg/kg bw in combination with systemic adverse effects. It was concluded that the NOAEL regarding reproduction was 1000 mg/kg bw/d and the NOAEL regarding development was found to be 300 mg/kg bw/d.

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

Please refer to the attached read-across justification in section 13.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Version / remarks:

1996

Deviations:

no

Sex:

male/female

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no statistically significant changes regarding reproductive performance

Key result

Critical effects observed:

no

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

viability

mortality

Key result

Critical effects observed:

no

Key result

Reproductive effects observed:

yes

Lowest effective dose / conc.:

1 000 mg/kg bw/day (actual dose received)

Treatment related:

yes

Relation to other toxic effects:

reproductive effects as a secondary non-specific consequence of other toxic effects

Dose response relationship:

yes

Conclusions:

Adverse effects regarding development were observed with the read across-substance (CAS 107-66-4) at 1000 mg/kg bw in combination with systemic adverse effects. It was concluded that the NOAEL regarding reproduction was 1000 mg/kg bw/d and the NOAEL regarding development was found to be 300 mg/kg bw/d.

Executive summary:

In order to investigate the toxicity of the read across substance (CAS 107-66-4) after repeated administration a combined repeated dose toxicity and reproductive toxicity study was undertaken using SD (Crj:CD(SD)) rats. There were 10 male and 10 female rats per group, and the test item doses were 0 (control: solvent administered), 30, 100, 300 and 1000 mg/kg bw/day, administered by forced oral administration every day from 14 days prior to the start of mating, until day 3 of lactation after delivery for the females (40-51 days), and for 44 days for the males. The results obtained were as follows: For the parental animals, no adverse effects due to test item administration were observed in the 30 mg/kg bw/day group (=NOAEL for systemic toxicity). With regard to reproduction of the parental males and parental females, no significant difference to the control group was observed for any of the indicators, even in the 1000 mg/kg bw/d group. One animal in the 1000 mg/kg bw/d group had a difficult delivery where all the pups died, and therefore the gestation index tended to be slightly low, but there were no significant changes. Regarding development of the pups, also in the 100 mg/kg bw/d and higher dose groups there were parental females whose pups all died: in the 1000 mg/kg bw/d group the incidence was high in that there were 3 such parental females, and so the number of live pups, the number of live pups on day 4 of lactation and the viability decreased or tended to be low. Although the only statistically significant difference observed was in the number of live female pups on day 4 of lactation, there was a decrease in the number of live pups, including males, on day 4 of lactation, and the viability was low. In the parental females whose pups all died, erosion and ulceration of the stomach were observed and severe pathological changes were confirmed, but no abnormalities of the pituitary or reproductive organs were observed. The changes in these developmental toxicity indicators in the parental females are therefore deemed to have been secondary general toxicological effects. It was concluded that the NOAEL regarding reproduction was 1000 mg/kg bw/d and the NOAEL regarding development was found to be 300 mg/kg bw/d.

Effect on fertility: 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:

GLP and guideline study

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In order to investigate the toxicity of the read across-substance (CAS 107 -66 -4) after repeated administration a combined repeated dose toxicity and reproductive toxicity study was undertaken using SD (Crj:CD(SD)) rats. There were 10 male and 10 female rats per group, and the test item doses were 0 (control: solvent administered), 30, 100, 300 and 1000 mg/kg bw/day, administered by forced oral administration every day from 14 days prior to the start of mating, until day 3 of lactation after delivery for the females (40-51 days), and for 44 days for the males. The results obtained were as follows: For the parental animals, no adverse effects due to test item administration were observed in the 30 mg/kg bw/day group (=NOAEL for systemic toxicity). With regard to reproduction of the parental males and parental females, no significant difference to the control group was observed for any of the indicators, even in the 1000 mg/kg bw/d group. One animal in the 1000 mg/kg bw/d group had a difficult delivery where all the pups died, and therefore the gestation index tended to be slightly low, but there were no significant changes. Regarding development of the pups, also in the 100 mg/kg bw/d and higher dose groups there were parental females whose pups all died: in the 1000 mg/kg bw/d group the incidence was high in that there were 3 such parental females, and so the number of live pups, the number of live pups on day 4 of lactation and the viability decreased or tended to be low. Although the only statistically significant difference observed was in the number of live female pups on day 4 of lactation, there was a decrease in the number of live pups, including males, on day 4 of lactation, and the viability was low. In the parental females whose pups all died, erosion and ulceration of the stomach were observed and severe pathological changes were confirmed, but no abnormalities of the pituitary or reproductive organs were observed. The changes in these developmental toxicity indicators in the parental females are therefore deemed to have been secondary general toxicological effects. It was concluded that the NOAEL regarding reproduction was 1000 mg/kg bw/d and the NOAEL regarding development was found to be 300 mg/kg bw/d.

Effects on developmental toxicity

Description of key information

In the above mentioned study conduicted with the read across-substance (CAS 107-66-4) the changes in developmental toxicity indicators (decreased pup viability, increased number of stillborn pups) in the parental females are deemed to have been secondary general toxicological effects. It was concluded that the NOAEL regarding reproduction was 1000 mg/kg bw/d and the NOAEL regarding development was found to be 300 mg/kg bw/d.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

GLP and Guideline study

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Available data on toxicity to reproduction and developmental toxicity indicate adverse effects on reproduction/development only together with general toxicity, thus not fulfilling requirements for classification under Regulation (EC) No 1272/2008 (CLP). Therefore, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelth time in Regulation (EU) No 2019/521.