Registration Dossier

Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Limited documentation of study methods (purity of test substance not given).

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1972
Report Date:
1972

Materials and methods

Principles of method if other than guideline:
Rodent Dominant Lethal Test.
GLP compliance:
no
Type of assay:
rodent dominant lethal assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): sorbitol, FDA 71-31

Test animals

Species:
rat
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
Acute-single dose procedure: once a week over 8 weeks, no further details given
Subacute-multipe dose procedure: 7 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
2500, 5000, 30000 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
Varying between 16 and 20, depending on dose group and treatment week (no further details given).
Control animals:
yes
Positive control(s):
triethylenemelamine (TEM)
- Doses / concentrations: 0.2 mg/kg bw

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Table 1: Average implantations per pregnant female

Week of study

Control

TEM

2500 mg/kg bw

5000 mg/kg bw

30000 mg/kg bw

Acute-Single Dose

1

236/19=12.4

193/19=10.2*

214/17=12.6

234/19=12.3

197/16=12.3

2

220/20=11

159/19=8.4*

250/20=12.5

227/19=11.9

234/20=11.7

3

209/20=10.5

170/20=8.5

254/20=12.7**I

210/18=11.7

212/20=10.6

4

230/20=11.5

60/18=3.3*

239/20=12

213/19=11.2

199/20=10

5

214/20=10.7

191/19=10.1

231/20=11.6

202/16=12.6**I

267/20=13.4**I

6

236/20=11.8

227/20=11.4

234/20=11.7

235/20=11.8

222/20=11.1

7

239/20=12

230/20=11.5

240/20=12

238/20=11.9

236/20=11.8

8

224/20=11.2

213/20=10.7

164/16=10.3

219/20=11.5

252/20=12.6*I

Subacute-Multiple Dose

1

 

 

215/17=12.6

207/18=11.5

242/19=12.7

2

 

 

190/19=10

224/20=11.2

195/17=11.5

3

 

 

236/20=11.8

239/20=12

209/20=10.5

4

 

 

236/20=11.8

211/17=12.4

247/20=12.4

5

 

 

254/19=13.4**I

255/20=12.8**I

236/18=13.1**I

6

 

 

246/20=12.3

186/19=9.8

191/17=11.2

7

 

 

212/18=11.8

237/19=12.5

215/20=10.8

* significant at p<0.05

** significant at p<0.01

I increase above control

Table 2: Average dead implants per pregnant female

Week of study

Control

TEM

2500 mg/kg bw

5000 mg/kg bw

30000 mg/kg bw

Acute-Single Dose

1

18/19=0.95

75/19=3.95**

18/17=1.06

8/19=0.42

20/16=1.25

2

11/20=0.55

135/19=7.11**

6/20=0.3

11/19=0.58

11/20=0.55

3

18/20=0.9

144/20=7.2**

19/20=0.95

7/18=0.39

17/20=0.85

4

19/20=0.95

58/18=3.22**

29/20=1.45

17/19=0.89

15/20=0.75

5

15/20=0.75

62/19=3.26**

18/20=0.9

5/16=0.31

12/20=0.6

6

22/20=1.10

41/20=2.05*

9/20=0.45*D

11/20=0.55

16/20=0.8

7

24/20=1.2

26/20=1.3

12/20=0.6

15/20=0.75

24/20=1.2

8

11/20=0.55

18/20=0.9

17/16=1.06

11/19=0.58

28/16=1.4

Subacute-Multiple Dose

1

 

 

9/17=0.53

20/18=1.11

12/19=0.63

2

 

 

15/19=0.79

11/20=0.55

11/17=0.65

3

 

 

14/20=0.70

15/20=0.75

13/20=0.65

4

 

 

6/20=0.3

26/17=1.53

24/20=1.2

5

 

 

11/19=0.58

25/20=1.25

17/18=0.94

6

 

 

13/20=0.65

8/19=0.42

19/17=1.12

7

 

 

11/18=0.61

11/19=0.58

20/20=1

* significant at p<0.05

** significant at p<0.01

D decrease below control

Table 3: Dead implants/total implants

Week of study

Control

TEM

2500 mg/kg bw

5000 mg/kg bw

30000 mg/kg bw

Acute-Single Dose

1

18/236=0.08

75/193=0.39**

18/214=0.08

8/234=0.03

20/197=0.1

2

11/220=0.05

135/159=0.85**

6/250=0.02*D

11/227=0.05

11/234=0.05

3

18/209=0.09

144/170=0.85**

19/254=0.07

7/210=0.03

17/212=0.08

4

19/230=0.08

58/60=0.97**

29/239=0.12

17/213=0.08

15/199=0.08

5

15/214=0.07

62/191=0.32**

18/231=0.08

5/202=0.02

12/267=0.04

6

22/236=0.09

41/227=0.18

9/234=0.04

11/235=0.05

16/222=0.07

7

24/239=0.10

26/230=0.11

12/240=0.05

15/238=0.6

24/236=0.10

8

11/224=0.05

18/213=0.08

17/164=0.1*

11/219=0.05

28/252=0.11

Subacute-Multiple Dose

1

 

 

9/215=0.04

20/207=0.1

12/242=0.05

2

 

 

15/190=0.08

11/224=0.05

11/195=0.06

3

 

 

14/236=0.06

15/239=0.06

13/209=0.06

4

 

 

6/236=0.03

26/211=0.12

24/247=0.10

5

 

 

11/254=0.04

25/255=0.1

17/236=0.07

6

 

 

13/246=0.05

8/186=0.04

19/191=0.10

7

 

 

11/212=0.05

11/237=0.05

20/215=0.09

* significant at p<0.05

** significant at p<0.01

D decrease below control

Table 4: Average corpora lutea per pregnant female

Week of study

Control

TEM

2500 mg/kg bw

5000 mg/kg bw

30000 mg/kg bw

Acute-Single Dose

1

252/19=13.3

252/19=13.3

233/17=13.7

257/19=13.5

216/16=13.5

2

254/20=12.7

220/19=11.6

278/20=13.9

244/19=12.8

257/20=12.9

3

244/20=12.2

247/20=12.4

271/20=13.6*I

230/18=12.2

264/20=13.2

4

260/20=13

227/18=12.6

267/20=13.4

250/19=13.2

237/20=11.9

5

244/20=12.2

234/19=12.3

252/20=12.6

210/16=13.1*I

277/20=13.9*I

6

265/20=13.3

253/20=12.7

270/20=13.5

253/20=12.7

247/20=12.4

7

259/20=13

250/20=12.5

271/20=13.6

267/20=13.4

248/20=12.4

8

242/20=12.1

258/20=12.9

203/16=12.7

237/19=12.5

260/20=13

Subacute-Multiple Dose

1

 

 

235/17=13.8

235/18=13.1

250/19=13.2

2

 

 

251/19=13.2

260/20=13

210/17=12.4

3

 

 

265/20=13.3

269/20=13.5*I

243/20=12.2

4

 

 

266/20=13.3

226/17=13.3

278/20=13.9

5

 

 

280/19=14.7**I

268/20=13.4*I

247/18=13.7**I

6

 

 

262/20=13.1

225/19=11.8*

206/17=12.1*

7

 

 

236/18=13.1

243/19=12.8

257/20=12.9

* significant at p<0.05

** significant at p<0.01

I increase above control

Table 5: Average preimplantation loss per pregnant female

Week of study

Control

TEM

2500 mg/kg bw

5000 mg/kg bw

30000 mg/kg bw

Acute-Single Dose

1

16/19=0.84

59/19=3.11*

19/17=1.12

23/19=1.21

19/16=1.19

2

34/20=1.7

61/19=3.21*

28/20=1.4

17/19=0.89

23/20=1.15

3

35/20=1.75

77/20=3.85*

17/20=0.85

20/18=1.11

52/20=2.6

4

30/20=1.5

167/18=9.28**

28/20=1.4

37/19=1.95

38/20=1.9

5

30/20=1.5

43/19=2.26

21/20=1.05

8/16=0.5

10/20=0.5*D

6

29/20=1.45

26/20=1.30

36/20=1.80

18/20=0.9

25/20=1.25

7

20/20=1

20/20=1

31/20=1.55

29/20=1.45

12/20=0.6

8

18/20=0.9

45/20=2.25

39/16=2.44

18/19=0.95

8/20=0.4

Subacute-Multiple Dose

1

 

 

20/17=1.18

28/18=1.56

8/19=0.42

2

 

 

61/19=3.21

36/20=1.8

15/17=0.88

3

 

 

29/20=1.45

30/20=1.5

34/20=1.7

4

 

 

30/20=1.50

15/17=0.88

31/20=1.55

5

 

 

26/19=1.37

13/20=0.65

11/18=0.61

6

 

 

16/20=0.8

39/19=2.05

15/17=0.88

7

 

 

24/18=1.33

6/19=0.32

42/20=2.1

* significant at p<0.05

** significant at p<0.01

D decrease below control

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative