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

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

K1 GLP OECD 422 test

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.

 

REPRODUCTION AND BREEDING DATA OF PARENTAL ANIMALS

 

At 500 mg/kg/day, an slight increased post natal loss was seen that was not statistically different than the control group.

 

At 20 and 100 mg/kg/day, no test item-related effects were observed in the reproduction and breeding data.

 

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.

 

FINDINGS IN PUPS AT FIRST LITTER CHECK AND DURING LACTATION

 

No test item-related abnormal findings were noted at the first litter check or during the first 4 days post partum. Sex ratios at the first litter check and on day 4 post partum were unaffected by exposure to the test item.

 

BODY WEIGHTS OF PUPS TO DAY 4 POST PARTUM

 

Mean pup weights were unaffected by treatment of the females with the test item.

 

MACROSCPICAL FINDINGS OF PUPS

 

No macroscopic findings were observed in pups at necropsy.

 

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. The NOAEL for reproduction/developmental toxicity was also considered to be 500 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:
Key study

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

K1 GLP OECD 422 test.

Additional information

OECD Acute Oral 422

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.

 

REPRODUCTION AND BREEDING DATA OF PARENTAL ANIMALS

 

At 500 mg/kg/day, an slight increased post natal loss was seen that was not statistically different than the control group.

 

At 20 and 100 mg/kg/day, no test item-related effects were observed in the reproduction and breeding data.

 

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.

 

FINDINGS IN PUPS AT FIRST LITTER CHECK AND DURING LACTATION

 

No test item-related abnormal findings were noted at the first litter check or during the first 4 days post partum. Sex ratios at the first litter check and on day 4 post partum were unaffected by exposure to the test item.

 

BODY WEIGHTS OF PUPS TO DAY 4 POST PARTUM

 

Mean pup weights were unaffected by treatment of the females with the test item.

 

MACROSCPICAL FINDINGS OF PUPS

 

No macroscopic findings were observed in pups at necropsy.

 

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. The NOAEL for reproduction/developmental toxicity was also considered to be 500 mg/kg bw/day.

Justification for selection of Effect on developmental toxicity: via oral route:
key study

Justification for classification or non-classification

Overall, the data obtained from the OECD422 reproductive and developmental toxicity screening test did not identify an effect on fertility, reproductive performance, development and viability of the offspring overs days 1 to 5 of lactation at dose levels up to and including 500 mg/kg bw/day. Therefore, it is considered that Isostearamide DEA should not be classified for reproduction toxicity.