Fatty acids, C16-18 and C18-unsatd., branched and linear, reaction products with diethanolamine

Endpoint summary

Description of key information

A subacute toxicity study was performed to assess the repeated dose toxicity of Isostearamide DEA. The study was an OECD 422 ‘combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test’ in which males were exposure for at least 28 days and females were exposed for ~ 7 weeks. From the results presented in this report a parenteral No Observed Adverse Effect Level (NOAEL) of 100 mg/kg/day was established. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

OECD 422 Acute Oral Study

The purpose of this study was to generate preliminary information concerning the effects of Isostearamide DEA on the possible health hazards likely to arise from repeated exposure over a relatively limited period of time. In addition it provided information on possible effects on male and female reproductive performance such as gonadal function, mating behavior, conception, development of the conceptus and parturition.

Isostearamide DEA was administered to male rats for at least 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum.

The following dose levels were applied:

Group 1:     0 mg/kg body weight/day (control group)

Group 2:   20 mg/kg body weight/day

Group 3: 100 mg/kg body weight/day

Group 4: 500 mg/kg body weight/day

A standard dose volume of 5 mL/kg body weight with a daily adjustment to the actual body weight was used. Control animals were dosed with the vehicle alone (corn oil).

The following results were obtained:

 

MORTALITY AND GENERAL TOLERABILITY OF PARENTAL ANIMALS

 

One female in the control group died spontaneously on day 11 of the pre-pairing period. All other animals survived their scheduled study period.

 

At 500 mg/kg/day, salivation was recorded in males and females during the study as well as ruffled fur in one male and one female for one day each.

 

No further clinical signs of toxicological relevance were recorded.

 

FUNCTIONAL OBSERVATIONAL BATTERY IN PARENTAL ANIMALS

 

No test item-related effects were observed from the functional observational battery or locomotor activity in males and females at any dose level.

 

FOOD CONSUMPTION OF PARENTAL ANIMALS

 

There were no differences of toxicological relevance between the mean food consumption of test item-treated or control males or females.

 

BODY WEIGHTS OF PARENTAL ANIMALS

 

There were no differences of toxicological relevance between the mean body weights of test item-treated or control males or females.

 

CLINICAL LABORATORY INVESTIGATIONS IN PARENTAL ANIMALS

 

No changes in hematology parameters of toxicological relevance were observed at any dose level.

 

An increased albumin and decreased globulin concentration observed in males treated at 500 mg/kg/day was considered to be test item-related. As a consequence of these changes the albumin / globulin ratio was also increased.

 

No changes of toxicological relevance in biochemistry parameters were observed in males treated at 20 and 100 mg/kg/day or in females at any dose level.

 

 

ORGAN WEIGHTS OF PARENTAL ANIMALS

 

Increased absolute and relative (to body weight) liver and kidney weights were recorded in males treated at 500 mg/kg/day. Increased liver weights relative to body weight were also recorded in females treated at this dose level.

 

No effects of the treatment with the test item on organ weights were recorded in animals treated at 20 and 100 mg/kg/day.

 

MACROSCOPICAL FINDINGS AND HISTOPATHOLOGY EXAMINATION OF PARENTAL ANIMALS

 

At macroscopical examination, the incidence of enlarged livers was increased in males treated at 500 mg/kg/day.

 

Microscopical examination revealed centrilobular hepatocellular hypertrophy at minimal to slight severity in both males and females treated at 500 mg/kg/day. This lesion was considered to be of metabolic nature and adaptive character.

 

In addition, there was an increased incidence of hyaline droplets in the kidneys in males at this dose level. These hyaline droplets were considered to be induced by overload of synthetic protein, that’s specific in male rat like as alpha-2 microglobrin, derived from hyperfunction of the liver.

 

No other test item-related findings were observed in males or females at any dose level.

 

 Conclusion

 

Based on these results, a NOAEL (No Observed Adverse Effect Level) for general toxicity in males and females was considered to be 100 mg/kg bw/day. In addition, due to a low vapor pressure (1e-3 Pa), a low water solubility (5.5e-5 g/L) and a log Kow of 6.46, absorption via inhalation and dermal routes is likely to be quite low. Therefore, the effects seen via oral dosing are likely to represent the worst case scenerio.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Key study

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
A data waiver has been submitted to address this endpoint.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
A data waiver has been submitted to address this endpoint.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
A data waiver has been submitted to address this endpoint.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
A data waiver has been submitted to address this endpoint.

Justification for classification or non-classification

Classification according to Regulation (EC) No 1272/2008.

Classification of substances for STOT-RE is normally based on a 90-day repeat dose study. When a study of a shorter duration of treatment is used for classification the guidance values is adjusted on a case-by-case basis and a NOAEL derived from a 28 day study is increased by a factor of 3. The guidance values for classification are based on the presence of significant toxic effects. None of the effects seen in the OECD 422 study were considered signficant or severe. Therefore, with regard to specific target organ toxicity – repeated exposure (STOT-RE), no classification is warranted. In addition, due to a low vapor pressure (1e-3 Pa), a low water solubility (5.5e-5 g/L) and a log Kow of 6.46, absorption via inhalation and dermal routes is likely to be quite low. Therefore, the effects seen via oral dosing are likely to represent the worst case scenerio.