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Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

A NOEL for reproductive toxicity of 1000 mg/kg bw/day was established for Phosphoric acid, C12 -18 -alkyl esters, potassium salts based on read-across information from an OECD 422 guideline study with Phosphoric acid, dodecyl ester, sodium salt.

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
Refer to attached document
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: mating index; fertility index; number of implantation sites; duration of pregnancy; birth index; live birth index; pregnancy index; litter size; other: estrous cycle, days to copulation, copulation rate
Key result
Dose descriptor:
NOEL
Generation:
F1
Effect level:
>= 1 000 mg/kg bw/day
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: litter size; litter weight; pup weight; sex ratio; viability index; other: external anomaly rate, necropsy findings
Key result
Reproductive effects observed:
no
Conclusions:
A NOEL for reproductive toxicity of 1000 mg/kg bw/day was established for Phosphoric acid, C12-18-alkyl esters, potassium salts based on read-across information from an OECD 422 guideline study with Phosphoric acid, dodecyl ester, sodium salt.
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:
Read-across from a study according to OECD 4422 Guideline with GLP
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Available data fromPhosphoric acid, dodecyl ester, sodium saltwere used to evaluate effects on reproductive toxicity ofPhosphoric acid, C12-18-alkyl esters, potassium salts.

 

In a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test according to OECD guideline 422 Phosphoric acid, dodecyl ester, sodium salt was administered to 12 Sprague-Dawley rats/sex/dose by daily oral gavage at dose levels of 0 (control), 250, 500, and 1000 mg/kg bw/day.

The males were exposed 14 days before mating, through the mating period, up to 1 day before termination (42 days in total). The females were exposed 14 days before mating, through the mating and gestation period, up to day 4 of lactation (42 to 45 days in total).

 

Administration of the test substance did not have any effect on the estrous cycle, days to copulation, copulation rate, fertility rate, or conception rate. Similarly, administration of the test substance did not have any effect on the delivery rate, gestation period, number of corpora lutea, number of implantation sites, implantation rate, stillbirth rate, number of live-born pups, live-birth rate in the mother animals, or on the sex ratio of the littermates. No abnormalities were observed in the lactating behavior during the lactation period either. These results suggest that administration of the test substance even at 1000 mg/kg had no effect on the reproductive function, such as that shown by the copulation rate, of the males or females, or in the fertility rate, conception rate, or on the gestation maintenance, delivery, or lactating behavior in the mother animals.

Pups showed no changes caused by the administration of the test substance regarding the observation at birth, necropsy findings on day 4 of lactation, body weight, or viability rate, which suggested that administration of the test substance even at 1000 mg/kg had no effect on the development.

 

The reproduction, breeding and developmental NOEL is 1000 mg/kg bw/d.

 

Justification for read-across

Evaluation of structure-activity relationship is based on data from structural similar substances with the same basic structure, salts of phosphoric acid alkyl ester, varying mainly in the chain length of fatty acid moiety. A detailed justification document for the read-across is attached in the respective target records of IUCID.

Effects on developmental toxicity

Description of key information

A NOEL for reproductive toxicity of 1000 mg/kg bw/day was established for Phosphoric acid, C12-18-alkyl esters, potassium salts based on read-across information from an OECD 422 guideline study with Phosphoric acid, dodecyl ester, sodium salt.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
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

Reproductive toxicity of Phosphoric acid, C12-18-alkyl esters, potassium salts was assessed based on data from a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening study with the read-across substance Phosphoric acid, dodecyl ester, sodium salt.

 

The no-observed-effect-level (NOEL) for systemic toxicity and also for reproductive/ developmental toxicity was considered to be 1000 mg/kg/day, the highest tested dose.

Considering the available data it can be concluded, that according to GHS Regulation EC No 1272/2008 classification for reproductive toxicity is not warranted for Phosphoric acid, C12-18-alkyl esters, potassium salts.

 

Additional information

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