Fatty acids, tall-oil, magnesium salts

Endpoint summary

Key value for chemical safety assessment

Effects on developmental toxicity

Description of key information

The hazard assessment of the substance is based on read across from Tall oil and 2-ethylhexanoic acid. The developmental toxicity study on 2 -EHA reveals effects on fertility that justifies a classification as repro. 2 according to the CLP regulation (EU) 1272/2008. The classification of 2 -EHA is harmonised through the EU. This classification is based on a NOAEL value for developmental toxicity of 100 mg/kg bw/day. This NOAEL value represent the most sensitive endpoint for the target substance (Reaction mass of Fatty acid, tall oil, 2 -ethylhexanoic acid and magnesium salts) and thus forms the basis for risk characterisation and safety assessment. There are no scientific reasons indicating that the constituents /of the substance can interact in a way that will influence the toxicological/ecotoxicological properties of the substance.

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4900 (Prenatal Developmental Toxicity Study)

GLP compliance:

yes

Species:

rat

Strain:

Fischer 344

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at arrival: males: 70 days; females: 63 days
- Weight at study initiation: males: 175-200 g; females: 130-150 g
- Housing: stainless steel wire mesh cages
- Diet (e.g. ad libitum): Prolab Certified Ground Rodent Chow, RMH-3200; ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 69-72
- Humidity (%): 45-65
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
The test chemical was diluted in certified corn oil (Mazola, Best Foods, Inc., CPC International) and mixed by inversion prior to the onset of the study. GC analysis indicated that the test material was stable for at least 21 days when stored at room temperature and uniformly distributed in corn oil. A dose volume of 2 ml/kg bodyweight (concentration in vehicle: 0 - 250 mg/ml) was administered by gavage, based on the body weight of each animal on gestation day 6.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Actual concentrations of test material in corn oil were determined by GC analysis and were 50.4, 132.0 and 246.0 mg/ml for the 100, 250 and 500 mg/kg/day doses, respectively. Analysis values ranged from 92.5 to 109.7% of the nominal dosing concentrations.

Details on mating procedure:

- Impregnation procedure: cohoused
- M/F ratio per cage: 1:1
- Each male was used only once
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy (GD 0)
- Successfully mated females weighing 147-174 g were housed singly and were randomly assigned (stratified by body weight) to each experimental group.

Duration of treatment / exposure:

Gestation day 6 through 15

Frequency of treatment:

Daily

Duration of test:

Up to gestation day 21

Dose / conc.:

0 mg/kg bw/day (nominal)

Dose / conc.:

100 mg/kg bw/day (nominal)

Dose / conc.:

250 mg/kg bw/day (nominal)

Dose / conc.:

500 mg/kg bw/day (nominal)

No. of animals per sex per dose:

25 (females only)

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: based on dose range finding study

Maternal examinations:

CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: on GD 0, 6 (prior to dosing), 12, 15, 18 and 21.

FOOD CONSUMPTION: Yes
- Food consumption (g food/animal/day) was measured for the intervals GD 0-3, 3-6, 6-9, 9-12, 12-15, 15-18 and 18-21.

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21 (CO2)
- Gross examination: gravid uterus, ovaries (including corpora lutea), cervix, vagina and abdominal and thoracic cavities.
- Organ weights: liver, uterus
- The liver was fixed for possible future examination

Ovaries and uterine content:

The uterus was externally examined for signs of hemorrhage, removed from the abdominal cavity and dissected longitudinally to expose the contents. All live and dead fetuses and resorption sites were noted and recorded. Uteri from females that appeared nongravid were placed in ammonium sulfide for detection of early resorptions.

Fetal examinations:

All live fetuses were weighed and sexed. All fetuses were examined for external malformations including cleft palate and variations. One half of the fetuses in each litter were examined for thoracic and abdominal visceral abnormalities. These fetuses were decapitated and their heads were fixed for examination of craniofacial structures. Remaining fetuses were eviscerated, fixed and examined for skeletal malformations and variations. Decapitated fetuses were also processed for staining but were not examined.

Statistics:

The unit of comparison was the pregnant female or the litter. Results of the quantitative continuous variables were intercompared for the dose groups by the Levene's test for equal variances, ANOVA, and t-tests with Bonferroni probabilities for pairwise comparisons. When Levene's test indicated homogeneous variances and the ANOVA was significant, the pooled t-test was used. When Levene's test indicated heterogeneous variances, all groups were compared by ANOVA for unequal variances followed, when necessary, by the separate variance t-test. Nonparametric data obtained following laparohysterectomy were treated using the Kruskal-Wallis test followed by the Mann-Whitney U test when appropriate. Incidence data were compared using Fisher's Exact Test.

Details on maternal toxic effects:

Details on maternal toxic effects:
Clinical signs were observed at the high-dose level only and included hypoactivity, ataxia, audible respiration, ocular discharge and periocular encrustations. No effects on body weight and mortality were observed. Liver weight (absolute and relative) was increased in the high-dose group.

Key result

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Key result

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:
Fetal body weights per litter were reduced in the high-dose group, but these findings may be confounded by the slightly larger mean litter size in this group. Reduced skeletal ossification was observed in the mid- and high-dose group. Dilation of the lateral ventricles of the brain with no tissue compression and extra (14th) thoracic centrum and arches were observed in all groups but were significantly increased at the high dose only.

Key result

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: Developmental toxicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Conclusions:

NOAEL for maternal toxicity was decided to be 250 mg/kg bw/day wheras the NOAEL for developmental toxicty was decided to be 100 mg/kg bw/day.

Reference 2

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

See attached file for justification of read across.

Reason / purpose for cross-reference:

read-across source

Details on maternal toxic effects:

Details on maternal toxic effects:
Clinical signs were observed at the high-dose level only and included hypoactivity, ataxia, audible respiration, ocular discharge and periocular encrustations. No effects on body weight and mortality were observed. Liver weight (absolute and relative) was increased in the high-dose group.

Key result

Dose descriptor:

NOAEL

Effect level:

250 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: Maternal toxicity

Key result

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: Developmental toxicity

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:
Fetal body weights per litter were reduced in the high-dose group, but these findings may be confounded by the slightly larger mean litter size in this group. Reduced skeletal ossification was observed in the mid- and high-dose group. Dilation of the lateral ventricles of the brain with no tissue compression and extra (14th) thoracic centrum and arches were observed in all groups but were significantly increased at the high dose only.

Key result

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: Developmental toxicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Justification for classification or non-classification

Because of the harmonised classification of 2-ethylhexanoic acid, the substance is classified as Repr 2.with the hazard phrase H361.