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EC number: 238-874-2 | CAS number: 14806-72-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction: other studies
Administrative data
- Endpoint:
- toxicity to reproduction: other studies
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2006-11-06 to 2008-01-10
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study is the result of a structural analogue substance used as read-across substance. Study is conducted according to Guidelines in a GLP certified laboratory.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 007
- Report date:
- 2007
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 415 (One-Generation Reproduction Toxicity Study)
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of method:
- in vivo
Test material
- Reference substance name:
- -
- EC Number:
- 427-360-5
- EC Name:
- -
- IUPAC Name:
- 427-360-5
- Details on test material:
- Description: Light Yellow Solid
Stability of test compound: Stable
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- - Males: The test item was administered during a 70-day pre-pairing period, during the pairing period and until necropsy
- Females: The test item was administered during a 14-day pre-pairing period and also during the pairing, gestation and lactation periods until necropsy - Frequency of treatment:
- Once daily
- Duration of test:
- Total duration of the test was 120 days
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0 (control), 100, 300 and 1000 mg/kg bw/day
Basis:
nominal in water
- No. of animals per sex per dose:
- 24 animals per sex per dose
- Control animals:
- yes, concurrent vehicle
Results and discussion
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 300 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
Observed effects
Any other information on results incl. tables
There were no mortalities or clinical signs observed in parental animals from any group. Males treated with 1000 mg/kg bw/day had significantly decreased food consumption during the first 15 days of the pre-pairing period. Mean body weight and mean body weight gain were also reduced during the first 20 days of the pre-pairing period. Food consumption, body weight and body weight gain of females was not affected by treatment with the test item.
For males at 1000 mg/kg bw/day, the mean liver body weight ratio was statistically significantly increased and was considered to be test item related. An increase in post-implantation loss was seen in females treated with 1000 mg/kg bw/day and this was considered to be possibly test item related.
There was no increase in mortality or clinical signs observed in the F1 pups following treatment with the test item. Mean pup weight was not affected by treatment. Additionally, during the macroscopic examination of pups no abnormal findings that were considered to be related to treatment with the test item were noted.
Table 1: Summary of food consumption of males
Days |
Group 1 (0 mg/kg bw/day) |
Group 2 (100 mg/kg bw/day) |
Group 3 (300 mg/kg bw/day) |
Group 4 (1000 mg/kg bw/day) |
||||
|
Food consumption (g) |
% of control |
Food consumption (g) |
% of control |
Food consumption (g) |
% of control |
Food consumption (g) |
% of control |
Pre-pairing period |
||||||||
1 - 8 |
23.6 ± 1.5 |
- |
23.4± 1.3 |
-0.8 |
22.9 ± 1.3 |
-3.0 |
22.5 ± 1.1** |
-4.7 |
8 - 15 |
24.4 ± 1.7 |
- |
24.1 ± 1.6 |
-1.2 |
23.6 ± 1.9 |
-0.8 |
22.8 ± 1.4** |
-0.8 |
15 - 22 |
24.4 ± 1.9 |
- |
24.2 ± 2.0 |
-0.8 |
23.7 ± 1.8 |
-2.9 |
23.7 ± 1.4 |
-2.9 |
22 - 29 |
24.2 ± 2.0 |
- |
24.0 ± 1.9 |
-0.8 |
23.7 ± 1.8 |
-2.1 |
23.7 ± 1.5 |
-2.1 |
29 - 36 |
23.9 ± 2.1 |
- |
24.2 ± 1.7 |
-1.3 |
23.7 ± 1.9 |
-0.8 |
23.7 ± 1.3 |
-0.8 |
36 - 43 |
23.8 ± 1.6 |
- |
24.0 ± 1.7 |
-0.8 |
23.6 ± 2.0 |
-0.8 |
23.7 ± 1.3 |
-0.4 |
43 - 50 |
23.6 ± 1.9 |
- |
23.4 ± 1.7 |
-0.8 |
23.3 ± 1.7 |
-1.3 |
23.6 ± 1.3 |
+0.0 |
50 - 57 |
24.5 ± 2.0 |
- |
24.6 ± 2.0 |
-0.4 |
24.4 ± 2.1 |
-0.4 |
25.1 ± 1.4 |
+2.4 |
57 - 64 |
24.2 ± 1.9 |
- |
24.3 ± 1.7 |
+0.4 |
24.2 ± 1.9 |
+0.0 |
24.3 ± 1.3 |
+0.4 |
64 - 70 |
24.7 ± 2.0 |
- |
24.6 ± 1.8 |
-0.4 |
24.5 ± 1.9 |
-0.8 |
24.8 ± 1.5 |
+0.4 |
After pairing period |
||||||||
1 - 8 |
23.9 ± 3.3 |
- |
24.3 ± 1.7 |
+1.7 |
24.6 ± 2.0 |
+2.9 |
24.4 ± 1.4 |
+2.1 |
8 - 15 |
24.2 ± 2.0 |
- |
23.5 ± 1.7 |
-2.9 |
24.2 ± 1.9 |
+0.0 |
23.7 ± 1.4 |
-2.1 |
15 - 19 |
24.1 ± 2.4 |
- |
24.0 ± 1.8 |
-0.4 |
24.8 ± 2.5 |
+2.9 |
24.9 ± 1.5 |
+3.3 |
* p<0.05, ** p<0.01
Table 2: Summary of food consumption of females
Days |
Group 1 (0 mg/kg bw/day) |
Group 2 (100 mg/kg bw/day) |
Group 3 (300 mg/kg bw/day) |
Group 4 (1000 mg/kg bw/day) |
||||
|
Food consumption (g) |
% of control |
Food consumption (g) |
% of control |
Food consumption (g) |
% of control |
Food consumption (g) |
% of control |
Pre-pairing period |
||||||||
1 - 8 |
18.0± 1.2 |
- |
17.5± 1.4 |
-2.8 |
17.2± 1.2 |
-4.4 |
17.2± 1.2 |
-4.4 |
8 - 14 |
18.7± 1.4 |
- |
18.3± 1.7 |
-2.1 |
17.8± 1.3 |
-4.8 |
18.1± 1.4 |
-4.4 |
Gestation period |
||||||||
1 - 7 |
22.2± 2.7 |
- |
22.2± 2.0 |
+0.0 |
22.4± 2.1 |
+0.9 |
22.5± 1.9 |
+1.4 |
7 - 14 |
24.1± 2.6 |
- |
24.0± 2.1 |
-0.5 |
24.1± 2.1 |
+0.0 |
24.5± 2.2 |
+1.7 |
14 - 21 |
25.7±2.4 |
- |
25.0± 2.6 |
-2.7 |
25.9± 1.9 |
+0.8 |
26.0± 2.1 |
+1.1 |
Lactation period |
||||||||
1 - 7 |
36.0± 3.9 |
- |
36.5± 6.0 |
+1.4 |
36.4± 3.8 |
+1.1 |
36.6± 4.6 |
+1.7 |
7 - 14 |
55.6± 4.3 |
- |
54.7± 8.7 |
-1.6 |
57.2± 3.9 |
+2.9 |
54.4± 5.0 |
-2.2 |
Table 3: Summary of body weights (g) and body weight gain (%) of males
Days |
Group 1 (0 mg/kg bw/day) |
Group 2 (100 mg/kg bw/day) |
Group 3 (300 mg/kg bw/day) |
Group 4 (1000 mg/kg bw/day) |
||||
|
Body weight (g) |
Body weight gain (%) |
Body weight (g) |
Body weight gain (%) |
Body weight (g) |
Body weight gain (%) |
Body weight (g) |
Body weight gain (%) |
Pre-pairing period |
||||||||
1 |
203 ± 9.4 |
0 |
203± 8.1 |
0 |
201 ± 8.5 |
0 |
202± 8.1 |
0 |
8 |
243 ± 11.9 |
19 |
241 ± 10.2 |
19 |
237 ± 14.9 |
18 |
236 ± 11.2 |
17* |
15 |
276 ± 15.3 |
36 |
272 ± 14.2 |
34 |
267 ± 21.2 |
33 |
262 ± 16.1* |
30** |
22 |
303 ± 18.9 |
49 |
300 ± 19.0 |
48 |
296 ± 25.8 |
47 |
289 ± 18.8 |
43 |
29 |
325 ± 21.1 |
60 |
322 ± 22.0 |
59 |
319 ± 28.6 |
59 |
311 ± 21.5 |
54 |
36 |
342 ± 23.3 |
68 |
339 ± 23.8 |
67 |
326 ± 32.0 |
67 |
327 ± 23.1 |
62 |
43 |
357 ± 25.0 |
76 |
354 ± 26.0 |
75 |
353 ± 36.2 |
76 |
345 ± 23.8 |
71 |
50 |
369 ± 25.9 |
82 |
366 ± 28.1 |
81 |
365 ± 36.8 |
82 |
356 ± 25.5 |
76 |
57 |
383 ± 27.9 |
88 |
380 ± 29.9 |
88 |
381 ± 38.0 |
89 |
369 ± 25.5 |
83 |
64 |
393 ± 29.8 |
94 |
389 ± 30.4 |
92 |
391 ± 39.6 |
95 |
378 ± 27.9 |
87 |
70 |
401 ± 30.6 |
97 |
396 ± 31.4 |
96 |
399 ± 40.8 |
99 |
384 ± 28.7 |
90 |
Pairing period |
||||||||
1 |
398 ± 31.4 |
0 |
392 ± 31.1 |
0 |
395 ± 42.7 |
0 |
379 ± 28.8 |
0 |
8 |
406 ± 30.5 |
2 |
401 ± 31.2 |
2 |
407 ± 40.4 |
3* |
390 ± 28.0 |
3* |
15 |
414 ± 31.9 |
4 |
409 ± 31.7 |
4 |
418 ± 41.5 |
6** |
399 ± 31.0 |
5 |
18 |
418 ± 31.7 |
5 |
414 ± 32.2 |
6 |
422 ± 41.7 |
7** |
403 ± 30.7 |
6 |
After pairing period |
||||||||
1 |
419 ± 32.1 |
0 |
415 ± 32.3 |
0 |
423 ± 41.8 |
0 |
403 ± 29.9 |
0 |
8 |
422 ± 33.1 |
1 |
419 ± 33.2 |
1 |
428 ± 42.9 |
1 |
402 ± 30.1 |
0 |
15 |
428 ± 33.6 |
2 |
427 ± 34.2 |
3 |
436 ± 43.5 |
3 |
411 ± 30.1 |
2 |
19 |
432 ± 36.1 |
3 |
430 ± 35.3 |
4 |
440 ± 44.8 |
4 |
412 ± 29.5 |
2 |
* p<0.05, ** p<0.01
Table 4: Summary of body weights (g) and body weight gain (%) of females
Days |
Group 1 (0 mg/kg bw/day) |
Group 2 (100 mg/kg bw/day) |
Group 3 (300 mg/kg bw/day) |
Group 4 (1000 mg/kg bw/day) |
||||
|
Body weight (g) |
Body weight gain (%) |
Body weight (g) |
Body weight gain (%) |
Body weight (g) |
Body weight gain (%) |
Body weight (g) |
Body weight gain (%) |
Pre-pairing period |
||||||||
1 |
157 ± 9.4 |
0 |
159± 6.1 |
0 |
157 ± 6.1 |
0 |
157 ± 8.7 |
0 |
8 |
176 ± 10.1 |
12 |
175 ± 8.1 |
11 |
174 ± 8.3 |
11 |
173 ± 9.4 |
10 |
14 |
188 ± 12.7 |
20 |
186 ± 7.9 |
18 |
184 ± 9.1 |
17 |
186 ± 9.8 |
18 |
Pairing period |
||||||||
1 |
193 ± 13.4 |
0 |
193 ± 8.1 |
0 |
192 ± 8.1 |
0 |
191 ± 8.1 |
0 |
8 |
208 |
17 |
205 ± 9.4 |
10 |
- |
- |
- |
- |
15 |
- |
- |
218 |
13 |
- |
- |
- |
- |
18 |
- |
- |
229 |
19 |
- |
- |
- |
- |
Gestation period |
||||||||
1 |
195 ± 12.2 |
0 |
197 ± 10.4 |
0 |
192 ± 10.9 |
0 |
193 ± 8.9 |
0 |
8 |
230 ± 15.1 |
18 |
231 ± 13.5 |
17 |
229 ± 13.5 |
20 |
229 ± 11.8 |
18 |
15 |
264 ± 20.1 |
36 |
264 ± 15.9 |
34 |
262 ± 15.8 |
37 |
264 ± 15.9 |
37 |
19 |
308 ± 23.5 |
58 |
307 ± 21.3 |
56 |
309 ± 18.2 |
62 |
309 ± 20.3 |
60 |
Lactation period |
||||||||
1 |
240 ± 19.7 |
0 |
237 ± 14.3 |
0 |
241 ± 15.9 |
0 |
244 ± 13.8 |
0 |
8 |
268 ± 19.2 |
12 |
269 ± 19.0 |
13 |
269 ± 13.4 |
12 |
270 ± 13.7 |
11 |
15 |
288 ± 19.8 |
20 |
291 ± 19.1 |
23 |
290 ± 14.0 |
21 |
291 ± 17.8 |
19 |
21 |
280 ± 19.1 |
17 |
286 ± 16.8 |
21* |
288 ± 12.0 |
20 |
291 ± 15.8* |
19 |
Table 5: Breeding data per group
|
Group 1 (0 mg/kg bw/day) |
Group 2 (100 mg/kg bw/day) |
Group 3 (300 mg/kg bw/day) |
Group 4 (1000 mg/kg bw/day) |
Litters |
23 |
24 |
23 |
24 |
Duration of gestation (days) |
21.5 ± 0.51 |
21.5 ± 0.51 |
21.3 ± 0.49 |
21.5 ± 0.51 |
Implantations |
13.0 ± 2.04 |
12.9 ± 2.97 |
13.2 ± 1.91 |
13.3 ± 1.78 |
Post implantation loss |
0.5 ± 0.95 |
0.7 ± 0.86 |
0.7 ± 0.88 |
1.8 ± 1.86* |
Dead pups at first litter check Litters affected (#) Total number of pups |
1 1 |
0 0 |
1 1 |
2 8 |
Living pups at first litter check % of males/females Mean ± SD |
53/47 12.5 ± 2.02 |
47/53 12.2 ± 2.79 |
45/55* 12.6 ± 1.80 |
45/55* 11.5 ± 2.55 |
Postnatal loss days 0-4 p.p. as % of living pups Litters affected (#) Total number of pups |
1.0 3 3 |
0.3 1 1 |
2.4 5 7 |
1.5 3 4 |
Breeding loss days 5-21 p.p. as % of living pups Litters affected (#) Total number of pups |
0.0 0 0 |
0.5 1 1 |
0.0 0 0 |
0.0 0 0 |
Birth index |
96.0 |
94.5 |
95.1 |
86.5** |
Viability index |
99.0 |
99.7 |
97.6 |
98.5 |
Weaning index |
100.0 |
99.5 |
100.0 |
100.0 |
Applicant's summary and conclusion
- Conclusions:
- The NOEL for parental animals and F1 pups was established at 300 mg/kg bw/day, based on reductions in food consumption, body weight gain and liver body weight ratio in males, and increased post-implantation loss in females.
- Executive summary:
The potential of Read Across substance 2 (RA2) to induce reproductive toxicity was investigated in a one-generation reproduction toxicity study. RA2 was administered to groups of Wistar rats (24/sex/dose) at the following doses: 0, 100, 300 and 1000 mg/kg bw/day. The test item was administered once daily to males for a 70 day pre-pairing period, during the pairing period and until the last litter had reached day 4 post partum. Females received the test item during a 14 day pre-pairing period and also during the pairing, gestation and lactation periods.
Parental rats were regularly monitored for mortality and clinical signs twice a day. Body weight was recorded daily from the start of treatment until necropsy. Food consumption was recorded weekly. All parental animals were subjected to gross necropsy, with particular attention to the organs of the reproductive system. Histopathological observations were carried out on the following organs for all high dose and control parental animals: pituitary glands, adrenals, uterus, oviducts, cervix, ovaries, testes with epididymides, prostate, seminal vesicles with coagulating glands, vagina, target organs. Histopathology was also performed on the reproductive organs of all infertile animals and on all gross lesions from all animals.
Reproductive and litter parameters assessed included: pregnant females during the first/second pairing period, number of females delivering pups, not mated/not pregnant, number of females rearing pups to weaning, duration of gestation, implantation rate, post-implantation loss, litter size, postnatal loss, breeding loss, abnormal findings at birth/during lactation/at macroscopic examination, pup weights after birth and sex ratios.
There were no mortalities or clinical signs observed in parental animals from any group. Males treated with 1000 mg/kg bw/day had significantly decreased food consumption during the first 15 days of the pre-pairing period. Mean body weight and mean body weight gain were also reduced during the first 20 days of the pre-pairing period. Food consumption, body weight and body weight gain of females was not affected by treatment with the test item.
For males at 1000 mg/kg bw/day, the mean liver body weight ratio was statistically significantly increased and was considered to be test item related. An increase in post-implantation loss was seen in females treated with 1000 mg/kg bw/day and this was considered to be possibly test item related.
There was no increase in mortality or clinical signs observed in the F1 pups following treatment with the test item. Mean pup weight was not affected by treatment. Additionally, during the macroscopic examination of pups no abnormal findings that were considered to be related to treatment with the test item were noted.
The NOEL for parental animals and F1 pups was therefore established at 300 mg/kg bw/day.
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