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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

In the oral study according to OECD 422 with the Source Substance 2, docosanoic acid, no developmental no reproductive effects were observed. The NOAEL of the study was 1000 mg/kg bw/d, means the highest dose tested did not cause adverse effects.

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
The functional group of the source substance docosanoic acid and the target substance is similar. Both substances are long chain acids which have no other funcitional group. Based on the similar structure and therefore similar expected toxicokinetic it is likely that the test result of this substance is also valid for the Category member (Please see attached Category Approach.)
Reason / purpose for cross-reference:
read-across source
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Immunological findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
- Males: no deaths or abnormalities in general condition were observed in any of the treated groups
- Females: no deaths were observed in any treated group

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
Males: significant increase (p<0.01) compared to control was observed in 100 mg/kg group between 8 - 15 days and between 15 - 29 days. However, since no change was observed in other groups, the effect was not considered to be related to the dosing of compound. No changes in food consumption related to the dosing of compound were observed
- Females: no significant changes in body weight were noted and there were no changes related to the dosing of compound in body weight gain and food consumption. A significant decrease (p<0.01) compared to control was observed during lactation in 100 mg/kg dosing group. However, since no other changes in food consumption were noted in 300 mg/kg and 1000 mg/kg dosing groups, the effect was not considered to be related to the dosing of compound.

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
There were no significant differences in number of corpora lutea, implantation rate, number of implantations and all other reproductive parameters in all treated groups compared to the control group.

ORGAN WEIGHTS (PARENTAL ANIMALS)
Males: in 100 mg/kg bw males, the actual weight ratio of liver weight (p <0.05) compared to control values were increased. No other significant differences were found in all groups. Thus, this finding lacks a dose-dependency and was regarded as incidental.
- Females: kidney weight was significantly reduced (p<0.05) in the 300 mg/kg bw group. No other weight changes were noted. Thus, this finding lacks a dose-dependency and was regarded as incidental.

GROSS PATHOLOGY (PARENTAL ANIMALS)
Males:
- Heart: myocardial degeneration was noted in one animal of the control group and the 1000 mg/kg bw group, respectively
- Liver: periportal fatty change of the liver was found in all animals of the control and the high dose group. Focal necrosis was noted in one animal of the high-dose group.
- Spleen: all animals of the control and the high-dose group showed brown pigment deposits of the spleen as well as extramedullary haematopeiosis
- Kidney: while fibrosis was only found in 1/13 animals of the control group, eosinophilic bodies and basophilic tubuli in the cortex were noted in animals of both control and high dose groups, respectively
- Adrenal gland: one animal of the high-dose group showed fibrosis
- Testis: atrophy of the seminiferous tubules was observed in two animals of the 1000 mg/kg dose group, with one animal affected on both sides and one side affected in the other animal. No other abnormalities were noted.
- Epididymis: abnormal sperm granuloma was found in one animal of the control group
- Brain: no abnormal findings noted
- Thymus: no abnormal findings noted
- Bladder: no abnormal findings noted

Females:
- Brain: one animal of the high-dose group showed abnormal mineral deposition in the thalamus
- Liver: focal necrosis and fibrosis was found in one animal of the control group, while one animal of the high-dose group showed only focal necrosis
- Spleen: brown pigmentation and extramedullary haematopeiosis was found in animals of the control and the high-dose group, but no varying degrees of frequency was observed
- Thymus: atrophy and bleeding was observed in animals of both groups, control and high-dose group, respectively
- Kidney: basophilic tubuli of the cotex and a dilatation of the renal pelvis was seen in the control and high-dose group
- Adrenal gland: cortical necrosis was observed in one animal of the control group
- Heart: no abnormal findings noted
- Bladder: no abnormal findings noted
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse substance -related findings on fertility were noted
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Immunological findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed
Remarks on result:
not determinable due to adverse toxic effects at highest dose / concentration tested
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Other effects:
no effects observed
Behaviour (functional findings):
no effects observed
Developmental immunotoxicity:
no effects observed
VIABILITY (OFFSPRING)
No change in number of birth, birth rate, infant live birth rate, infant survival and birth rates at day 4 was found in all dose groups compared to the values of the control group.

BODY WEIGHT (OFFSPRING)
No difference in bodyweight of pups of the dose groups and the control group was found.

GROSS PATHOLOGY (OFFSPRING)
No morphological abnormalities were found in all groups.
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed
Remarks on result:
not determinable due to adverse toxic effects at highest dose / concentration tested
Clinical signs:
not examined
Dermal irritation (if dermal study):
not examined
Mortality / viability:
not examined
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings:
not examined
Other effects:
not examined
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
Key result
Reproductive effects observed:
not specified

Table 1. Summary of development up of pups from dams treated orally with docosanoic acid in the combined repeat dose and reproductive/developmental toxicity screening test: Mean± S.D (N)

Dose group (mg/kg)

0

100

300

1000

Number of pregnant females

13

12

12

13

Number of pregnant females with live pups

13

12

12

13

Gestation index

100

100

100

100

Gestation length in days

22.2±0.4 (13)

22.4±0.5 (12)

22.3±0.5 (12)

22.2±0.4 (13)

Number of corpora lutea

16.6±1.6 (13)

16.7±1.8 (12)

16.8±2.3 (12)

16.2±1.5 (13)

Number of implantation sites

16.1±1.5 (13)

15.8±2.1 (12)

16.0±1.5 (12)

15.2±3.1 (13)

Implantation index

96.9±5.1 (13)

94.8±7.1 (12)

96.1±6.0 (12)

93.1±15.2 (13)

Day 0 of lactation

 

 

 

 

Number of pups born

15.2±1.6 (13)

14.8±2.2 (12)

15.2±1.5 (12)

14.3±2.7 (13)

Delivery index

94.5±8.0 (13)

93.5±3.9 (12)

94.9±4.3 (12)

94.9±6.2 (13)

Number of live pups

14.9±1.6 (13)

14.3±2.2 (12)

15.1±1.6 (12)

14.1±2.7 (13)

Birth index

93.1±8.8 (13)

90.7±8.7 (12)

94.3±5.1 (12)

93.5±7.2 (13)

Live birth index

98.5±2.8 (13)

97.0±8.5 (12)

99.4±2.2 (12)

98.5±4.0 (13)

Sex ration on day 0

50.0±11.3 (13)

46.7±9.8 (12)

54.8±12.3 (12)

48.9±13.4(13)

Day 4 of lactation

 

 

 

 

Number of live pups

14.7±1.4 (13)

13.0±4.7 (12)

15.1±1.6 (12)

14.1±2.7 (13)

Viability index

98.6±2.7 (13)

89.4±28.8 (12)

100.0±0.0 (12)

100.0±0.0 (13)

Sex ration on day 4

49.8±11.5 (13)

46.3±10.3 (11)

54.8±12.3 (12)

48.9±13.4(13)

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:
Klimisch 2
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 target substance and Category member 2, 2 -butyl octanoic acid, was investigated for developmental toxicity testing in rats. Mated female Sprague-Dawley rats were randomised into 4 treatment groups, each containing 25 animals. These animals were dosed orally by gavage once daily over Days 6-19 inclusive of gestation, where Day 0 was the day of detection of mating. The dose levels applied were 0 (control); 25; 200 and 400 mg/kg bw/d. In conclusion, under the conditions of this study, the maternal No Effect Level was considered to be 25 mg/kg bw/d and the foetal No Effect Level was considered to be 200 mg/kg bw/d. In not maternal toxic dosages no teratogenic effects were found. Therefore the substance is considered to be not developmental toxic. In the oral study according to OECD 422 with the Source Substance 2, docosanoic acid, no developmental no reproductive effects were observed. The NOAEL of the study was 1000 mg/kg bw/d, means the highest dose tested did not cause adverse effects.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Klmisch 2
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

Based on the available data the target substance and Category Member 2 does not need to be classified.

Additional information