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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

The reproductive toxicity of Diacid 1550, the free acid of the target substance, was investigated in a combined 28-d repeated dose toxicity/reproscreening study that was performed in accordance with OECD 422 and under GLP conditions. Diacid 1550 was administered orally via the diet at 0, 500, 3000, and 15000 ppm. Based on increased liver weights and increased centrilobular hepatocyte hypertrophy in males and females at the highest dose, the parental NOAEL was considered to be 3000 ppm., corresponding to 271 mg/kg bw/day of free acid, under the conditions of this study. Considering the change in molecular weight of the potassium salt, this value becomes corrected to 298 mg/kg bw/d to be used for hazard and risk assessment of the target substance, the corresponding potassium salt. However, reproductive parameters such as fertility and developmental effects were not affected by treatment and thus, the NOAEL was set to the high dose group, equivalent to a NOAEL of 1324 mg/kg bw/d, considering adjustment to the potassium salt, being 1454 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance fatty acids, tall-oil, reaction products with acrylic acid potassium salt is the corresponding potassium salt of the source substance fatty acids, tall-oil, reaction products with acrylic acid and manufactured accordingly by neutralisation with potassium hydroxide. As the potassium salt does not contribute to the genetic toxicity because it is an essential nutrient, a read-across to the free acids is justified.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance actually is manufactured form the source substance by neutralisation of fatty acids, tall-oil, reaction products with acrylic acid (source substance) with potassium hydroxide, forming the target substance fatty acids, tall-oil, reaction products with acrylic acids potassium salt. The source substance has been registered already. Toxicity to reproduction/developmental toxicity potential of Diacid 1550 was investigated in a combined 28-d repeated dose toxicity/reproscreening study that was performed in accordance with OECD 422 and under GLP conditions. Diacid 1550 was administered orally via the diet at 0, 500, 3000, and 15000 ppm. There were no treatment-related changes observed in reproductive parameters in any of the dose groups. Therefore, the NOAEL for reproductive parameters was considered 15000 ppm (corresponding to 1324 mg/kg bw/day), under the conditions of the performed study.
3. ANALOGUE APPROACH JUSTIFICATION
The structure of the organic moiety of source and target substance is identical and thus read-across form the free acid to its salt is common practice and justified.
4. DATA MATRIX
Not relevant here as organic moieties of source and target substance are identical, and both only do differ by the potassium cation present in the target substance (compared to a proton in the source substance).
Reason / purpose:
read-across source
Considering correction by molecular weight of the potassium salt having 363.1 g/mol as weighted average molecular weight, compared to 330.6 g/mol as weighted average molecular weight for the free acid, the NOAEL for parental animals of the source study, being 271 mg/kg bw/d can be corrected to the potassium salt as being 271 * 363.1/330.6 = 298 mg/kg bw/d, which is the adjusted NOAEL for the potassium salt.
Considering correction by molecular weight of the potassium salt having 363.1 g/mol as weighted average molecular weight, compared to 330.6 g/mol as weighted average molecular weight for the free acid, the NOAEL of the source study for reproductive parameters, being 1324 mg/kg bw/d can be corrected to the potassium salt as being 1324 * 363.1/330.6 = 1454 mg/kg bw/d, which is the adjusted NOAEL for the potassium salt.

Dose descriptor:
NOAEL
Effect level:
298 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Increased liver weights and increased centrilobular hepatocyte hypertrophy in males and females in the highest dose
Dose descriptor:
NOAEL
Effect level:
1 454 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: reproductive parameters
Considering correction by molecular weight of the potassium salt having 363.1 g/mol as weighted average molecular weight, compared to 330.6 g/mol as weighted average molecular weight for the free acid, the NOAEL of the source study, being 1324 mg/kg bw/d can be corrected to the potassium salt as being 1324 * 363.1/330.6 = 1454 mg/kg bw/d, which is the adjusted NOAEL for the potassium salt.
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 454 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: There were no treatment-related changes in reproductive parameters in any of the dose groups.
Reproductive effects observed:
not specified
Conclusions:
The reproductive toxicity of Diacid 1550, the free acid of the target substance, was investigated in a combined 28-d repeated dose toxicity/reproscreening study that was performed in accordance with OECD 422 and under GLP conditions. Diacid 1550 was administered orally via the diet at 0, 500, 3000, and 15000 ppm. Based on increased liver weights and increased centrilobular hepatocyte hypertrophy in males and females at the highest dose, the parental NOAEL was considered to be 3000 ppm., corresponding to 271 mg/kg bw/day of free acid, under the conditions of this study. Considering the change in molecular weight of the potassium salt, this value becomes corrected to 298 mg/kg bw/d to be used for hazard and risk assessment of the target substance, the corresponding potassium salt. However, reproductive parameters such as fertility and developmental effects were not affected by treatment and thus the NOAEL was set to the high dose group, equivalent to a NOAEL of 1324 mg/kg bw/d, considering adjustment to the potassium salt, being 1454 mg/kg bw/d.
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

The reproductive toxicity of Diacid 1550, the free acid of the target substance, was investigated in a combined 28-d repeated dose toxicity/reproscreening study that was performed in accordance with OECD 422 and under GLP conditions. Diacid 1550 was administered orally via the diet at 0, 500, 3000, and 15000 ppm. Based on increased liver weights and increased centrilobular hepatocyte hypertrophy in males and females at the highest dose, the parental NOAEL was considered to be 3000 ppm., corresponding to 271 mg/kg bw/day of free acid, under the conditions of this study. Considering the change in molecular weight of the potassium salt, this value becomes corrected to 298 mg/kg bw/d to be used for hazard and risk assessment of the target substance, the corresponding potassium salt. However, reproductive parameters such as fertility and developmental effects were not affected by treatment and thus, the NOAEL was set to the high dose group, equivalent to a NOAEL of 1324 mg/kg bw/d, considering adjustment to the potassium salt, being 1454 mg/kg bw/d.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
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

No reproductive effects (fertility/development) were seen in an OECD 422 screening study and thus, no classification for reproductive toxicity is required according to CLP (Regulation EC No 1272/2008).