Registration Dossier

Administrative data

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:
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

Justification for classification or non-classification