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EC number: 212-603-8 | CAS number: 831-52-7
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
Reproductive toxicity study
Based on the data available from different studies, NOAEL for test material was considered to be of 30 mg/kg bw/day for F0, F1 generation. When male and female rats were treated with test material orally. Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.
Link to relevant study records
- Endpoint:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data from peer reviewed journal
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- Teratology and percutaneous toxicity study of test material was performed on rats
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No data available
- Age at study initiation: No data available
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Mated females were housed individually in temperature- and humidity-controlled rooms.
- Diet (e.g. ad libitum): Ralston Purina Laboratory chow, ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimatization period: No data available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%): No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available - Route of administration:
- dermal
- Vehicle:
- other: 6% hydrogen peroxide
- Details on exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): No data available
- Concentration in vehicle: No data available
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Details on mating procedure:
- -Time-pregnant female rats were used.
-Presence of sperm in vagina considered day 0 of gestation - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 7 days
- Frequency of treatment:
- Every third day, i.e. on days 1, 4, 7, 10, 13, 16 and 19 of gestation
- Details on study schedule:
- No data available
- Remarks:
- 0.1 % (0.001316 mg/kg)
- No. of animals per sex per dose:
- Total: 100
Control 1: 20 female
Control 1: 20 female
Control 1: 20 female
0.001316 mg/kg : 20 female
Positive Control : 20 female - Control animals:
- yes
- Details on study design:
- Further details on study design
- Dose selection rationale: No data available
- Rationale for animal assignment (if not random): No data available
- Other: No data available - Positive control:
- acetylsalicylic acid
- Parental animals: Observations and examinations:
- -Animals were weighed on the day the dyes were administered.
-The uteri were examined, corpora lutea of pregnancy counted, and the number, distribution and location of live, dead, and resorbed fetuses were recorded - Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- Live fetuses and weight of fetuses were examined
- Postmortem examinations (parental animals):
- Number of Corpora lutea and number, distribution, and location of live, dead, and resorbed fetuses were examined.
- Postmortem examinations (offspring):
- -All fetuses were examined for gross anomalies, sexed, and weighed.
-One-third the fetuses from each litter were fixed in Bouin's solution and subsequently examined for visceral anomalies by razor blade sectioning.
-The remaining fetuses in each litter were fixed in 95% ethyl alcohol, eviscerated, cleared, stained with KOH-alizarin red S and examined for skeletal anomalies - Statistics:
- All statistical analyses compared the treatment groups with the control groups. The number of females exhibiting resorption sites, number of females exhibiting two or more resorptions, number of dead or resorbed fetuses, and the number of fetuses with soft-tissue or skeletal anomalies and accessory ribs was compared using chi-square test criterion with Yates' correction on 2 X 2 contingency tables as described by Steel and Torrie (1960) or Fisher's exact probability test (Siegel, 1956) as appropriate to judge the significance of difference. The mean number of corpora lutea, implantation sites, live fetuses, and resorption sites was compared by analysis of variance (one-way classification) as described by Steel and Torrie (1960) using Dunnett's (1964) multiple comparison tables to judge the significance of differences. The live fetal weights were compared by analysis of variance (hierarchal classification) as described by Steel and Torrie (1960) using Dunnett's (1964) multiple comparison tables to judge the significance of differences. Statistically significant differences between groups were judged valid only when there were significant differences between any one of the dye treated groups and each of the three untreated control groups.
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Changes in the color of the skin and hair at the site of dye application were observed in treated rats.
- Dermal irritation (if dermal study):
- no effects observed
- Description (incidence and severity):
- No irritation or other changes were observed in treated rats.
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No effect on body weight of treated rats was observed as compared to control.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No effect on food consumption of treated rats was observed as compared to control.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not examined
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- No significant effect on number of corpora lutea and implantation sites oftreated rats was observed as compared to control.No significant effect on live fetuses, sex ratio, resorption sites or mean resorptions per pregnancy oftreated rats was observed as compared to control.
- Dose descriptor:
- NOAEL
- Effect level:
- 0.001 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- dermal irritation
- body weight and weight gain
- food consumption and compound intake
- reproductive performance
- Remarks on result:
- other: No effects on reproductive performance was observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- No effect on Live fetuses was observed in treated female rats as compared to control.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No effect on body weight of fetuseswas observed in treated female rats as compared to control.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Description (incidence and severity):
- No significant soft-tissue anomalies were observed infetuses of treated female rats as compared to control.
Normally occurring accessory ribs variations were observed infetuses of treated female rats as compared to control. - Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 0.001 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- viability
- body weight and weight gain
- gross pathology
- histopathology: non-neoplastic
- Remarks on result:
- other: No toxic effects were observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- NOAEL was considered to be 0.001316 mg/kg for F0 and F1 geneartion when pregnent female CD rats were treatre wtih test material
- Executive summary:
In a Teratology study, pregnent female CD rats were treatre wtih test material in the concentration of 0 and 0.001316 mg/kg dermally in6% hydrogen peroxide on days 1, 4, 7, 10, 13, 16, and 19 of gestation. Acetylsalicylic acid were used as positive control. Changes in the color of the skin and hair at the site of dye application were observed in treated rats. No irritation or other changes were observed in treated rats.No effect on body weight and food consumption of treated rats was observed as compared to control. Similarly,No significant effects on number of corpora lutea, implantation sites, live fetuses, sex ratio, resorption sites or mean resorptions per pregnancy of treated female rats wereobserved as compared to control. In addition, No effect on body weight offetuseswas observedas compared to control. No significant soft-tissue anomalies were observed infetuses of treated female rats as compared to control.Normally occurring accessory ribs variations were observed infetuses of treated female rats as compared to control. Therefore, NOAEL was considered to be 0.001316 mg/kg for F0 and F1 geneartion when pregnent female CD rats were treatre wtih test material dermally on days 1, 4, 7, 10, 13, 16, and 19 of gestation.
Reference
Summary of Teratology Study in Rats Receiving P-21
Observations |
Control I Untreated |
Control II Untreated |
Control III Untreated |
Acetylsalicylic acid (250 mg/kg-day) |
P-21 (2 ml/kg) |
Maternal parameters |
|
|
|
|
|
Total no. females gravid |
20 |
20 |
20 |
20 |
20 |
Mean no. corpora lutea |
15.35 |
13.55 |
15.25 |
16.15° |
13.45 |
Mean no. implantation sites |
12.40 |
12.10c |
13.90 |
13.25 |
11.65° |
No. females exhibiting resorption Sites |
13 |
14 |
12 |
15 |
8 |
No. females exhibiting 2 ormore resorption sites |
9 |
7 |
6 |
15d |
4 |
No. females aborting |
0 |
0 |
0 |
0 |
0 |
Fetal parameters |
|
|
|
|
|
Mean no. live fetuses/group |
10.65 |
10.85 |
12.50 |
8.70c |
11.00 |
Mean live fetal weight (g) |
3.38 |
3.58 |
3.62 |
2.89e |
3.79f |
No. dead or resorbed fetuses (%) |
35(14.11) |
25(10.33) |
28 (10.07) |
91 (34.34)e |
13(5.58)f |
Mean no. resorptions/pregnancy |
1.75 |
1.25 |
1.40 |
4.5 5h,i |
0.65g |
Sex ratio, M:F |
106:107 |
102:115 |
119:131 |
100:75 |
116:104 |
No. fetuses with soft-tissueanomalies (%) |
4(6.35) |
4(6.06) |
6(7.79) |
21 (36.84)e |
7(10.29) |
No. fetuses with skeletal anomalies (%) |
0(0.00) |
1 (0.67) |
2(1.16) |
40(34.19)e |
1 (0.65) |
No. fetuses with accessory ribs only (%) |
75 (50.00) |
56(37.09) |
72 (41.62) |
32 (27.35) |
83 (54.60)b,h |
aSignificantly different from control II atp < 0.05.
bSignificantly different from control III at p < 0.05.
cSignificantly different from control III at p < 0.01.
dSignificantly different from controls II, III atp < 0.05.
eSignificantly different from controls I, I I , III atp < 0.01.
fSignificantly different from control I at p < 0.01.
gSignificantly different from control I atp < 0.05.
^Significantly different from control II atp <0.01.
'Significantly different from controls I, III atp < 0.05.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 30 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from authoritative database
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 0.001 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from authoritative database
Additional information
Reproductive toxicity study
Data available from different studies were reviewed to determine the reproductive toxicity of test chemical.The studies are as mentioned below:
Study 1
In a Teratology study, pregnent female CD rats were treatre wtih test materialin the concentration of 0 and 0.001316 mg/kg dermally in6% hydrogen peroxide on days 1, 4, 7, 10, 13, 16, and 19 of gestation. Acetylsalicylic acid were used as positive control. Changes in the color of the skin and hair at the site of dye application were observed in treated rats. No irritation or other changes were observed in treated rats.No effect on body weight and food consumption of treated rats was observed as compared to control. Similarly,No significant effects on number of corpora lutea, implantation sites, live fetuses, sex ratio, resorption sites or mean resorptions per pregnancy of treated female rats wereobserved as compared to control. In addition, No effect on body weight offetuseswas observedas compared to control. No significant soft-tissue anomalies were observed infetuses of treated female rats as compared to control.Normally occurring accessory ribs variations were observed infetuses of treated female rats as compared to control. Therefore, NOAEL was considered to be 0.001316 mg/kg for F0 and F1 geneartion when pregnent female CD rats were treatre wtih test materialdermallyon days 1, 4, 7, 10, 13, 16, and 19 of gestation.
Study2
In a reproductive and developmental toxicity study oftest material was assessed in femaleWistar derived SPF-Albino Crl:Wi/Br rats when they were exposed at concentration0, 10, 30 and 60 mg/kg bw/dayduring gestation period of 5-15 days.During the study the mortality, signs of intoxication, body weight and food consumption were recorded. All mated females were sacrified on day 20 of gestation. In the pregnant female, a complete autopsy and a macroscopic examination of the organs were carried out. Uterus were weighed and examined. For each ovary, corpora lutea were counted and foetuses were individually weighed and sexed. A gross examination of all foetuses was performed and one-third of the foetuses were examined for visceral anomalies. The other foetuses were evaluated for skeletal defects. No rats died during the treatment period. No toxic effects were reported during the study. Females of all dose groups had orange-brown discoloured urine throughout the application period at dose related intensity. Mean maternal bodyweight gains and mean food consumptions over the gestation period were normal when compared to the control group. Gross necropsy did not reveal any organ alterations related to treatment. No significant differences in the number of viable foetuses, the male to female sex ratio, birth- position, number of runts, post-implantation losses, implantations, resorptions and corpora lutea between dosage groups and the control group were observed. At 60mg/kg bw dose group showed an increase in foetal body weight and uteri weights with a tendency towards dose-relation. Examination of the foetuses yielded minor variations (wavy ribs) at comparable inter-group frequencies and incidences within the historical control animals of this strain. There were no biologically significant differences in the number of litters with malformations or developmental variations between any of the dose groups and the control group.HenceNOAEL was considered to be 30 mg/kg/day for test material in femaleWistar derived SPF-Albino Crl:Wi/Br rats when they were exposed at concentration0, 10, 30 and 60 mg/kg bw/dayduring gestation period of 5-15 days by oral gavage.
Study 3
In a Teratology study,New Zealand White female rabbits were treated with test materialin the concentration of0, 19.5 and 97.5 mg/kg/day orally by gavage fromday 6 to day 18 of gestation. Bluebrown colored urine were observed in all treated rabbits.
No adverse effect onbody weight gain, Number of pregnancies, numbers of corpora lutea, implantations, resorptions, and live and stillborn fetuses were observed in treated female rabbits. No effect on fetusesweight were observed in treated female rabbits. In addition, No gross abnormalities, visceral and skeletal abnormalities were observed in fetusesof treated female rabbits. Therefore, NOAEL was considered to be 97.5 mg/kg/day for F0 and F1 geneartion when New Zealand White female rabbits were treated with test materialorally by gavage for 13 days.
Study 4
Reproductive and developmental toxicity study of test materialwas performed on male and female CFE-Srats .20 male and 20 female rats /dose group were used.One male was mated with one female until copulation was confirmed by the presence of sperm during daily vaginal inspections (day 0 of pregnancy).The females then were weighed, transferred into individual cages.The test materialmixed with feed were administers in dose concentration 0, 97.5,616 mg/kg bw/day (0, 1950,7800 ppm)from day from day 6 through day 15. Pregnancy was further confirmed by biweekly weighing of the females. All females were killed by chloroform inhalation on the 19th day of pregnancy and the fetuses delivered by Caesarian section. The number and distribution of fetuses, and the number of corpora lutea, live and stillboin fetuses, and early and late resorptions were recorded. Each fetus was weighed, measured, and examined for gross abnormalities. One-third of each litter was examined for visceral abnormalities by employing the slicing method of Wilson (1965). The remaining two-thirds were cleared and the bone structure stained with alizarin red S in order to define any skeletal abnormalities (Murphy, 1965)
No dose-related significant differences were observed in the parameters examined. The 616mg/kg /day (7800 ppm) dose group excreted blue-brown colour urine.No grossly abnormal pups were noted in the 97.5 mg/kg /day dose group (244 pups); there was one in control group (244 pups). One grossly abnormal pup was noted out of the 262 examined in the 616 mg/kg /day dose group.however, the average numbers of implantation sites, live pups, and early or late resorptions were not significantly different among the groups. HenceNo Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 616 mg/kg/day (7800ppm.When male and femaleCFE-Srats were treated with test material orally.
Based on the data available from different studies ,test material did not showedreproductive toxicityat dose concentration 30 mg/kg body weight/day,when male and female rats were treated with test material orally,Thus, comparing this value with the criteria of CLP regulation test material is not likely to classify as reproductive toxicant.
Effects on developmental toxicity
Description of key information
Developmental toxicity study
Based on the various studies available for the test chemical were reviewed to determine the developmental toxicity, NOAELfor test chemical was considered to be 30 mg /kg bw/day .When rats were treated with test chemical orally. Thus, comparing this value with the criteria of CLP regulation test chemical is not likely to classify as reproductive and developmental toxicant.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data from peer reviewed journal
- Qualifier:
- according to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- Teratology study of test material in rats
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Charles River CD
- Details on test animals or test system and environmental conditions:
- - Source: No data available
- Age at study initiation: No data available
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Mated females were housed individually in temperature- and humidity-controlled rooms.
- Diet (e.g. ad libitum): Ralston Purina Laboratory chow, ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimatization period: No data available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%): No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available - Route of administration:
- dermal
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- other: 6% hydrogen peroxide
- Details on exposure:
- The hair-dye (2.0 mL/kg) was applied to the dorsocapsular area (shaved skin) of each animal on days 1, 4, 7, 10, 13, 16, and 19 of gestation
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Presence of sperm in vagina considered day 0 of gestation
- Duration of treatment / exposure:
- 20 days
- Frequency of treatment:
- Every third day, i.e. on days 1, 4, 7, 10, 13, 16 and 19 of gestation
- Remarks:
- Doses / Concentrations:
2.0 mL/kg of 0.1% (0.001316 mg/kg)
Basis:
no data - No. of animals per sex per dose:
- Total: 100
Control 1: 20 female
Control 1: 20 female
Control 1: 20 female
0.001316 mg/kg : 20 female
Positive Control : 20 female - Control animals:
- other: acetylsalicylic acid
- Maternal examinations:
- Animals were weighed on the day the dyes were administered.
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes:One-third of the fetuses from each litter were examined for visceral anomalies.
- Skeletal examinations: Yes:The remaining fetuses were examined for skeletal anomalies
- Head examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data - Statistics:
- All statistical analyses compared the treatment groups with the control groups.
The number of females exhibiting resorption sites, number of females exhibiting two or more resorptions, number of dead or resorbed fetuses, and the number of fetuses with soft-tissue or skeletal anomalies and accessory ribs was compared using chi-square test or Fisher's exact probability test as appropriate to judge the significance of difference.
The mean number of corpora lutea, implantation sites, live fetuses, and resorption sites was compared by analysis of variance (one-way classification) using Dunnett's multiple comparison tables to judge the significance of differences.
The live fetal weights were compared by analysis of variance (hierarchal classification) using Dunnett's multiple comparison tables to
judge the significance of differences.
Statistically significant differences between groups were judged valid only when there were significant differences between any one of the dye treated groups and each of the three untreated control groups - Indices:
- No data available
- Historical control data:
- No data available
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Changes in the color of the skin and hair at the site of dye application were observed in treated rats.
- Dermal irritation (if dermal study):
- no effects observed
- Description (incidence and severity):
- No irritation or other changes were observed in treated rats.
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No effect on body weight of treated rats was observed as compared to control.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No effect on food consumption of treated rats was observed as compared to control.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- not specified
- Other effects:
- not specified
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
No signs of toxicity were seen throughout the study. Except for the changes in the color of the skin and hair at the site of dye application, no irritation or other changes in appearance were seen.
Changes in female body weights were similar for rats in the untreated controls and all dye-treated groups.
A marked reduction in maternal weight gain through gestation was observed in the rats receiving acetylsalicylic acid as compared with either the untreated control rats or dye-treated rats.
Mean food consumption for all groups throughout gestation was similar except for rats in the acetylsalicylic acid group; these rats showed a moderate decrease in food consumption from days 7 to .13 of gestation.
The dye formulations produced no significant differences in the mean number of corpora lutea, implantation sites and live fetuses, and the sex ratio when compared with the untreated control groups.
No differences between groups were seen regarding the number of females exhibiting resorption sites or mean resorptions per pregnancy - Dose descriptor:
- NOAEL
- Effect level:
- 0.001 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- clinical signs
- early or late resorptions
- food consumption and compound intake
- pre and post implantation loss
- total litter losses by resorption
- Remarks on result:
- other: No effects on reproductive performance was observed
- Abnormalities:
- not specified
- Localisation:
- not specified
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- No effect on body weight of fetuseswas observed in treated female rats as compared to control.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- No significant soft-tissue anomalies were observed infetuses of treated female rats as compared to control.
Normally occurring accessory ribs variations were observed infetuses of treated female rats as compared to control. - Dose descriptor:
- NOEL
- Effect level:
- 0.001 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- reduction in number of live offspring
- changes in sex ratio
- external malformations
- skeletal malformations
- visceral malformations
- Remarks on result:
- other: No developmental toxic effects were observed
- Abnormalities:
- not specified
- Localisation:
- other: not specified
- Developmental effects observed:
- not specified
- Treatment related:
- not specified
- Relation to maternal toxicity:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- NOAEL was considered to be 0.001316 mg/kg for F0 and F1 geneartion when pregnent female CD rats were treatre wtih test material
- Executive summary:
In a Teratology study, pregnent female CD rats were treatre wtih test material in the concentration of 0 and 0.001316 mg/kg dermally in6% hydrogen peroxide on days 1, 4, 7, 10, 13, 16, and 19 of gestation. Acetylsalicylic acid were used as positive control. Changes in the color of the skin and hair at the site of dye application were observed in treated rats. No irritation or other changes were observed in treated rats.No effect on body weight and food consumption of treated rats was observed as compared to control. Similarly,No significant effects on number of corpora lutea, implantation sites, live fetuses, sex ratio, resorption sites or mean resorptions per pregnancy of treated female rats wereobserved as compared to control. In addition, No effect on body weight offetuseswas observedas compared to control. No significant soft-tissue anomalies were observed infetuses of treated female rats as compared to control.Normally occurring accessory ribs variations werewere observed infetuses of treated female rats as compared to control. Therefore, NOAEL was considered to bhe 0.001316 mg/kg for F0 and F1 geneartion when pregnent female CD rats were treatre wtih test material dermally on days 1, 4, 7, 10, 13, 16, and 19 of gestation.
Reference
Summary of Teratology Study in Rats Receiving P-21
Observations |
Control I Untreated |
Control II Untreated |
Control III Untreated |
Acetylsalicylic acid (250 mg/kg-day) |
P-21 (2 ml/kg) |
Maternal parameters |
|
|
|
|
|
Total no. females gravid |
20 |
20 |
20 |
20 |
20 |
Mean no. corpora lutea |
15.35 |
13.55 |
15.25 |
16.15° |
13.45 |
Mean no. implantation sites |
12.40 |
12.10c |
13.90 |
13.25 |
11.65° |
No. females exhibiting resorption Sites |
13 |
14 |
12 |
15 |
8 |
No. females exhibiting 2 ormore resorption sites |
9 |
7 |
6 |
15d |
4 |
No. females aborting |
0 |
0 |
0 |
0 |
0 |
Fetal parameters |
|
|
|
|
|
Mean no. live fetuses/group |
10.65 |
10.85 |
12.50 |
8.70c |
11.00 |
Mean live fetal weight (g) |
3.38 |
3.58 |
3.62 |
2.89e |
3.79f |
No. dead or resorbed fetuses (%) |
35(14.11) |
25(10.33) |
28 (10.07) |
91 (34.34)e |
13(5.58)f |
Mean no. resorptions/pregnancy |
1.75 |
1.25 |
1.40 |
4.5 5h,i |
0.65g |
Sex ratio, M:F |
106:107 |
102:115 |
119:131 |
100:75 |
116:104 |
No. fetuses with soft-tissueanomalies (%) |
4(6.35) |
4(6.06) |
6(7.79) |
21 (36.84)e |
7(10.29) |
No. fetuses with skeletal anomalies (%) |
0(0.00) |
1 (0.67) |
2(1.16) |
40(34.19)e |
1 (0.65) |
No. fetuses with accessory ribs only (%) |
75 (50.00) |
56(37.09) |
72 (41.62) |
32 (27.35) |
83 (54.60)b,h |
aSignificantly different from control II atp < 0.05.
bSignificantly different from control III at p < 0.05.
cSignificantly different from control III at p < 0.01.
dSignificantly different from controls II, III atp < 0.05.
eSignificantly different from controls I, I I , III atp < 0.01.
fSignificantly different from control I at p < 0.01.
gSignificantly different from control I atp < 0.05.
^Significantly different from control II atp <0.01.
'Significantly different from controls I, III atp < 0.05.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 30 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from authoritative database
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 0.001 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from authoritative database
Additional information
Developmental toxicity study
Data available from different studies for test chemicals were reviewed to determine the developmental toxicity of test chemical. The studies are as mentioned below:
Study 1
In a Teratology study, pregnent female CD rats were treatre wtih test materialin the concentration of 0 and 0.001316 mg/kg dermally in6% hydrogen peroxide on days 1, 4, 7, 10, 13, 16, and 19 of gestation. Acetylsalicylic acid were used as positive control. Changes in the color of the skin and hair at the site of dye application were observed in treated rats. No irritation or other changes were observed in treated rats.No effect on body weight and food consumption of treated rats was observed as compared to control. Similarly,No significant effects on number of corpora lutea, implantation sites, live fetuses, sex ratio, resorption sites or mean resorptions per pregnancy of treated female rats wereobserved as compared to control. In addition, No effect on body weight offetuseswas observedas compared to control. No significant soft-tissue anomalies were observed infetuses of treated female rats as compared to control.Normally occurring accessory ribs variations werewere observed infetuses of treated female rats as compared to control. Therefore, NOAEL was considered to bhe 0.001316 mg/kg for F0 and F1 geneartion when pregnent female CD rats were treatre wtih test materialdermallyon days 1, 4, 7, 10, 13, 16, and 19 of gestation.
Study 2
In a reproductive and developmental toxicity study oftest material was assessed in femaleWistar derived SPF-Albino Crl:Wi/Br rats when they were exposed at concentration0, 10, 30 and 60 mg/kg bw/dayduring gestation period of 5-15 days.During the study the mortality, signs of intoxication, body weight and food consumption were recorded. All mated females were sacrified on day 20 of gestation. In the pregnant female, a complete autopsy and a macroscopic examination of the organs were carried out. Uterus were weighed and examined. For each ovary, corpora lutea were counted and foetuses were individually weighed and sexed. A gross examination of all foetuses was performed and one-third of the foetuses were examined for visceral anomalies. The other foetuses were evaluated for skeletal defects. No rats died during the treatment period. No toxic effects were reported during the study. Females of all dose groups had orange-brown discoloured urine throughout the application period at dose related intensity. Mean maternal bodyweight gains and mean food consumptions over the gestation period were normal when compared to the control group. Gross necropsy did not reveal any organ alterations related to treatment. No significant differences in the number of viable foetuses, the male to female sex ratio, birth- position, number of runts, post-implantation losses, implantations, resorptions and corpora lutea between dosage groups and the control group were observed. At 60mg/kg bw dose group showed an increase in foetal body weight and uteri weights with a tendency towards dose-relation. Examination of the foetuses yielded minor variations (wavy ribs) at comparable inter-group frequencies and incidences within the historical control animals of this strain. There were no biologically significant differences in the number of litters with malformations or developmental variations between any of the dose groups and the control group.HenceNOAEL was considered to be 30 mg/kg/day for test material in femaleWistar derived SPF-Albino Crl:Wi/Br rats when they were exposed at concentration0, 10, 30 and 60 mg/kg bw/dayduring gestation period of 5-15 days by oral gavage.
Study3
In a Teratology study,CFE-S female rats were treated with test material in the concentration of 0, 195 and 616 mg/kg/day orally in diet fromday 6 to day 15 of gestation. No adverse effect onaverage number of implantation sites, live pups or in the number of females with one or more resorption sites were observed in treated female rats. No effect on fetuses weight were observed in treated female rats. In addition, No were gross abnormalities, visceral and skeletal abnormalities were observed in fetusesoftreated female rats. Therefore, NOAEL was considered to be 616mg/kg/day for F0 and F1 geneartion when CFE-S female rats were treated with test material orally in diet for 10 days.
Study 4
In a Teratology study,New Zealand White female rabbits were treated with test materialin the concentration of0, 19.5 and 97.5 mg/kg/day orally by gavage fromday 6 to day 18 of gestation. Bluebrown colored urine were observed in all treated rabbits.
No adverse effect onbody weight gain, Number of pregnancies, numbers of corpora lutea, implantations, resorptions, and live and stillborn fetuses were observed in treated female rabbits. No effect on fetusesweight were observed in treated female rabbits. In addition, No gross abnormalities, visceral and skeletal abnormalities were observed in fetusesoftreated female rabbits. Therefore, NOAEL was considered to be 97.5 mg/kg/day for F0 and F1 geneartion when New Zealand White female rabbits were treated with test material orally by gavage for 13 days.
Thus, based on the data available fortest chemical,No Observed Adverse Effect Level (NOAEL) was considered to be 30mg /kg bw .When rats were treated with test chemical orally. Thus, comparing this value with the criteria of CLP regulationtest chemicalis not likely to classify as reproductive and developmental toxicant.
Justification for classification or non-classification
Thus, comparing this value with the criteria of CLP regulation test chemical is not likely to classify as reproductive and developmental toxicant.
Additional information
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