11-methyldodecyl laurate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Read-across from supporting substance (8- metylnonyl octadec-9-enoate)

The experimental data obtained by testing 8-methylnonyl octadec-9-enoate can be reliably extrapolated (by read-across) to 11-methyldodecyl laurate and support the low toxicity of the substance.

Overall, 11-methyldodecyl laurate should not be classified for the reproductive/developmental toxicity in accordance with Regulation (EC) n. 1272/2008.

Furthermore, the study allows to suitably identify a NOAEL which can be used in the risk assessment.

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

Justification for type of information:

The justification for type of information is provided in attachment.

Reason / purpose for cross-reference:

read-across source

Clinical signs:

no effects observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

slight reduction in body weight and food consumption of the high dose females

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

slight reduction in body weight and food consumption of the high dose females

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

not examined

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

increase in post implantation loss, decrease in birth index, increase in the number of stillbirths (all high dose group)

CLINICAL SIGNS AND MORTALITY
Piloerection was seen in 1 female of the high dose group at on day 2-4 of lactation.

BODY WEIGHT AND WEIGHT GAIN AND FOOD CONSUMPTION
Reduction in body weight (-9.7%) in high dose females during lactation period. Reduction in food intake (-21.7%) in high dose females during gestation/lactation.

ORGAN WEIGHTS
All effects observed (slight increase in absolute and relative liver weight in males) were still within the historical control data of the laboratory and thus not of toxicological relevance.

GROSS PATHOLOGY
No effects observed.

HISTOPATHOLOGY
No effects observed.

REPRODUCTION
The qualitative sperm staging revealed no test item-related specific spermatogenic changes in the male animals from the high dose group (1000 mg/kg b.w./day).
- Pre-coital time: No effects observed
- Gestation length: No effects observed
- Reproduction parameters of the dams: statistically significant increase in post implantation loss, non-statistically significant decrease in birth index, elevated number of stillbirths, leading to a statistically significant reduction in the live birth index.
No effects were found for the fertility index, the gestation index and the preimplantation loss.

Key result

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: adverse effects on ody weight and body weight gain and food consumption at 1000 mg/kg bw/d

Key result

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: no adverse effects observed

Key result

Dose descriptor:

NOAEL

Remarks:

reproduction

Effect level:

300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: an increase in post-implantation loss, a decrease in the birth index and a decrease in the live birth index at 1000 mg/kg bw/d

Key result

Dose descriptor:

NOAEL

Remarks:

reproduction

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: no spermatogenic changes

Clinical signs:

no effects observed

Mortality / viability:

mortality observed, treatment-related

Description (incidence and severity):

reduces viability (high dose group)

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

reduced litter weight of the high dose female offspring

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

VIABILITY (OFFSPRING)
A test item-related decrease in the viability index was noted in the high dose group (1000 mg/kg bw/day) (71.3 % in the high dose group vs. 98.7% in the control group). The high number of dead pups in the high dose group was due to 2 dams with no surving pups on lactation day 4 (deaths partly due to cannibalization). The total litter loss in 2 of 7 dams (28.6%) was considered as test item related.

LITTER WEIGHT
A non-statistically significant reduction in mean litter weight on lactation day 1 by 17.2% was noted in the high dose group (high dose group), which is regarded to be test item-related. Total litter weight was also reduced by 24.4% in comparison to controls.

GROSS PATHOLOGY (OFFSPRING)
No effects observed.

Key result

Dose descriptor:

NOAEL

Remarks:

developmental

Generation:

F1

Effect level:

300 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: effects on litter weight and viability of the offspring at 1000 mg/kg bw/day.

Key result

Reproductive effects observed:

not specified

Individual body weights of females during the pre-mating and lactation period.

Control group	Day(s) relative to start
	1	8	15
11	196	209	212
12	217	228	243
13	210	220	213
14	217	234	244
15	3211	215	232
16	195	208	197
17	205	224	239
18	212	238	233
19	224	236	259
20	200	218	214
Mean	209	223	229
SD	9	10	19

1000 mg/kg bw	Day(s) relative to start
	1	8	15
71	200	210	225
72	210	231	234
73	206	234	247
74	210	222	235
75	194	219	218
76	218	243	223
77	214	230	227
78	222	225	210
79	198	200	201
80	203	223	231
Mean	207	224	225
SD	9	12	13

Control group	Day(s) relative to littering
	1	4
11	286	309
12	323	330
13	325	311
14	331	327
15	311	322
16	282	302
17	309	327
18	312	328
19	315	331
20	300	329
Mean	309	322
SD	16	10

1000 mg/kg bw	Day(s) relative to littering
	1	4
71	270	281
72	339	301
73	289	309
75	289	317
77	253	247
78	280	271
79	290	296
80	293	308
Mean	288	291
SD	24	23

Relative food consumption of females between day 1 and 4 of lactation

Control group		1000 mg/kg bw
11	122	71	115
12	91	72	96
13	105	73	63
14	107	75	110
15	106	77	30
16	121	78	63
17	114	79	98
18	100	80	110
19	101
20	126
Mean	109	Mean	86
SD	11	SD	30

Viability index [%], day 1 to 4 of lactation

Control group		1000 mg/kg bw
11	93	71	93
12	100	72	100
13	100	73	0
14	93	74	not pregnant
15	100	75	100
16	100	76	not pregnant
17	100	77	0
18	93	78	no viable pubs
19	89	79	100
20	100	80	100
Mean	96	Mean	70
SD	4	SD	48

Summary of Live Birth Index, Pre-implantation loss, and Post-implantation loss in female animals

	Control group	100 mg/kg bw	300 mg/kg bw	1000 mg/kg bw
Live Birth Index
Mean	100	100	100	86
SD	0	0	0	35
Total %^1	100	100	100	91
Pre-implantation loss
Mean	2.4	18.3	0.6	8.1
SD	3.1	26.0	2.0	9.8
Total %^2	2.5	20.3**	0.7	9.1*
Post-implantation loss
Mean	7.6	9.0	7.5	20.8
SD	10.5	14.8	8.8	32.9
Total %^3	7.6	10.2	7.7	21.7**

*:p < 0.05 / **: p < 0.01, Chi²-test

#1: based on the total number of live born pups and the total number of pups at birth (alive and dead)

#2: based on the total number of corpora lutea and the total number of implantation sites

#3: based on the total number of implantation sites and the total number of live born pups

 

 

Conclusions:

The experimental data obtained by testing 8-methylnonyl octadec-9-enoate can be reliably extrapolated (by read-across) to 11-methyldodecyl laurate and support the low toxicity of the substance.
Overall, 11-methyldodecyl laurate should not be classified for the reproductive/developmental toxicity in accordance with Regulation (EC) n. 1272/2008.
Furthermore, the study allows to suitably identify a NOAEL which can be used in the risk assessment.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

300 µg/kg bw/day

Study duration:

subchronic

Species:

rat