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EC number: 204-781-0 | CAS number: 126-30-7
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on generations indicated in Effect levels (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- The study was conducted according to OECD Guideline 422. GLP standards were fulfilled. Since a detailed report in English is not available (only in Japanese with tables in English) not all details of this study are documented but the data base is sufficient for evaluation. Acceptable restrictions: no data were given on historical control range for hematology and clinical chemistry of this laboratory; hematology & clinical chemistry only in males; no details about test animals, application volume and concentration, mating procedure, analysis of dose, and stability in vehicle. Data presented in the MHW SIDS dossier are partly contradictory to the original data in Biosafety Research 1993, e.g. organ weights in females.
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 993
- Reference Type:
- publication
- Title:
- JETOC Information sheet 2,2-Dimethyl-l,3-propanediol
- Author:
- JETOC
- Year:
- 1 995
- Bibliographic source:
- JAPAN CHEMICAL INDUSTRY ECOLOGY-TOXICOLOGY & INFORMATION CENTER, JETOC No.18, April, 1995, Tokyo, Japan
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- yes
- Remarks:
- (hematology and clinical chemistry only in males)
- GLP compliance:
- yes
- Remarks:
- Biosafety Research Center; Foods, Drugs and Pesticides, An-pyo Center, Japan
- Limit test:
- no
Test material
- Reference substance name:
- 2,2-dimethylpropane-1,3-diol
- EC Number:
- 204-781-0
- EC Name:
- 2,2-dimethylpropane-1,3-diol
- Cas Number:
- 126-30-7
- Molecular formula:
- C5H12O2
- IUPAC Name:
- 2,2-dimethylpropane-1,3-diol
- Details on test material:
- purity 99,15%
Main impurities: neopentyl glycol formic acid ester and neopentyl glycol isolactic acid ester (according to SIDS dossier)
No further data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Sprague-Dawley (slc:SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Housing condition
Temperature: 22-24°C
Rel. air humidity: 50-60%
Photoperiod: 12h/12h (150-300 lux)
No further details
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- No details available, especially no data on concentration in vehicle (distilled water) and application volume.
- Details on mating procedure:
- 12 pairs mated at each dose level; max. 6 conceiving days.
No further details. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Exposure period
Males: 45 days; females: from 14 days before mating to day 3 of lactation
Premating exposure period (males): not clearly stated but presumably ca. 6 weeks
Premating exposure period (females): 14 days
Duration of test: terminal kill for males at day 46 and females at day 4 of lactation - Frequency of treatment:
- once daily
- Details on study schedule:
- no further details
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 100, 300, 1000 mg/kg bw/d
Basis:
no data
but presumably actual ingested dose; 1000 mg/kg bw/day is the recommended limit dose according to OECD422
- No. of animals per sex per dose:
- 12 males and 12 females per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No further details
- Positive control:
- No
Examinations
- Parental animals: Observations and examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes (no details)
BODY WEIGHT: Yes
- Time schedule for examinations: Males day 0 and then once weekly during exposure period; females day 0, 7, 14 in premating period, day 0, 7, 14, 21 during gestation; day 1 and 4 in lactation period.
FOOD CONSUMPTION: Yes
No details
WATER CONSUMPTION: No data
HEMATOLOGY (only males)
all parameters recommended in OECD Guideline 422; no details about sampling.
CLINICAL CHEMISTRY (only males)
all parameters recommended in OECD 422 except sodium & cholesterol; no details about sampling. - Oestrous cyclicity (parental animals):
- yes, data recorded in all dose groups (no details).
- Sperm parameters (parental animals):
- No data available (not mandatory according to OECD422)
- Litter observations:
- Live pups at birth and at day 4; Sex ratio; litter & pup weight at birth and at day 4; loss of offsprings; abnormal pups
- Postmortem examinations (parental animals):
- Organ weights (absolute and relative) determined at termination. Not all organs recommended in OECD422 were presented in the result section (no details given in methods but presumably no effects detected on organ weights and therefor not included in the result section; presumably the examinations correspond to the Guideline).
Necropsy and histopathology performed. Not all organs recommended in OECD422 were presented in the result section (no details given in methods but presumably no effects detected in pathological examinations and examinations correspond to the Guideline). - Postmortem examinations (offspring):
- Termination at lactation day 4; external examinations.
- Statistics:
- No details about methods but statistical significance was calculated; limit of significance p<0.05.
Mean +- standard deviation (SD) was given. - Reproductive indices:
- Copulation index
Fertility index
Gestation index
Implantation index
Delivery index - Offspring viability indices:
- Birth index
Viability index on day 4
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Other effects:
- effects observed, treatment-related
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- effects observed, treatment-related
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
Details on results (P0)
-Clinical signs & mortality
No treatment-related clinical signs and no mortality was found in any group.
- Body weight and food consumption
of males and females in the treatment groups did not reveal any differences when compared to the control group.
- Hematology
No effects were detected in hematology of male rats.
- Clinical chemistry
revealed increased levels of total protein, total bilirubin and albumin among male rats receiving 300 and 1000 mg/kg bw/day and a decrease in glucose in male rats receiving 1000 mg/kg (no clinical chemistry in females). Other effects in clinical chemistry (see Table) were not considered by the authors to be of toxicological relevance (no dose dependency or within the standard deviation of the concurrent control).
- Organ weights
Absolute and relative weights of the liver of male rats receiving 300 and 1000 mg/kg bw/day were elevated. Absolute and relative kidney weights were elevated in male rats receiving 1000 mg/kg bw/day (see Table below). No effects were found in females (including liver and kidney).
Weights of reproductive organs were not affected in males (epididymides, testis) and females (ovaries).
- Necropsy & Histopathology
No effects detected in females.
Liver: In examinations of the liver hypertrophy was found in 2/12 male rats at 1000 mg/kg bw/day. However, histopathological examination revealed no definite associated lesion of the liver.
Kidney: Histopathological examination revealed increases in the amounts of protein casts, hyaline droplets and an increase in the severity in basophilic alteration of the renal tubular epithelium in male rats receiving 1000 mg/kg bw/day; data are presented in the Table below.
REPRODUCTIVE PERFORMANCE
Copulation was not altered by the treatment (see copulation index in the Table below); the number of pregnant rats after successful copulation was not reduced by the treatment (see fertility index); the estrus cycle was slightly but significantly (p<0.05) prolonged at 1000 mg/kg bw/day, however, the biological relevance is questionable (see also standard deviation corresponding to individual variance). Mean number of corpora lutea were not changed by the treatment (see Table below; Implantation index).
The following parameters were also not altered: Delivery index, Birth index, and Viability index post natal day 4 (see Table below).
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 100 mg/kg bw/day
- Sex:
- male
- Basis for effect level:
- other: repeated dose toxicity; authors evaluation in JETOC1995 without explanations (NOAEL not given)
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/kg bw/day
- Sex:
- male
- Basis for effect level:
- other: based on effects in the kidney of male rats at 1000 mg/kg bw/day.
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day
- Sex:
- female
- Basis for effect level:
- other: repeated dose toxicity; highest dose level tested
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: reproductive performance
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not specified
Details on results (F1)
No effects on duration of gestation, number of total implants, total born pups (live pups), sex ratio, loss of offspring, live pups at day 4, pup weight, and litter weight. External examination revealed no increase in abnormal pups to be caused by test substance (2 pups with trauma in the low dose group).
Results are presented in the Table below.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 1 000 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: developmental toxicity
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Blood chemistry in
males treated with neopentyl glycol
n=12
in each group
Parameter |
Dose in mg/kg bw/day |
|||
0 |
100 |
300 |
1000 |
|
Glucose (mg/dl) |
152+-7 |
154+-17 |
164+-26 |
140+-10** |
Total bilirubin (mg/dl) |
0.25+-0.02 |
0.26+-0.02 |
0.28+-0.02* |
0.32+-0.04** |
Blood urea nitrogen (mg/dl) |
15.5+-2.4 |
17.7+-4.4 |
18.2+-3.0 |
18.8+-2.6 |
Creatinine (mg/dl) |
0.64+-0.04 |
0.66+-0.08 |
0.69+-0.09 |
0.68+-0.06 |
Total protein (g/dl) |
6.02+-0.18 |
6.07+-0.11 |
6.29+-0.16** |
6.42+-0.19** |
Albumin (g/dl) |
3.25+-0.12 |
3.31+-0.09 |
3.46+-0.16** |
3.52+-0.14** |
Potassium (mmol/l) |
4.87+-0.23 |
4.52+-0.41* |
4.91+-0.38 |
4.72+-0.24 |
Chloride (mmol/l) |
105.5+-1.3 |
106.8+-1.8 |
106.5+-1.7 |
105.2+-1.2 |
Calcium (mmol/l) |
9.34+-0.31 |
9.64+-0.24* |
9.81+-0.42** |
9.67+-0.27* |
Inorganic phosphate (mg/dl) |
5.37+-0.67 |
5.75+-0.52 |
6.43+-0.96** |
5.68+-0.48 |
GOT (U/l) |
49+-10 |
38+-4** |
42+-10* |
43+-8 |
GPT (U/l) |
24+-5 |
21+-5 |
23+-3 |
20+-2 |
Gamma-GT (U/l) |
0.5+-0.4 |
1.4+-0.5** |
0.3+-0.5 |
0.5+-0.4 |
mean +-SD; *: p<0.05; **: p<0.01 |
x
x
x
Organ weights in males
treated with neopentyl glycol
n=12
in each group
Parameter |
Dose in mg/kg bw/day |
|||
0 |
100 |
300 |
1000 |
|
Body weight in g |
391+-23 |
395+-23 |
399+-27 |
392+-30 |
Thymus (absolute in mg) |
303+-70 |
333+-36 |
286+-57 |
313+-82 |
Liver (absolute in g) |
11.2+-1.15 |
11.5+-0.96 |
12.5+-1.18* |
13.1+-1.43** |
Kidney (absolute in g) |
2.61+-0.18 |
2.70+-0.16 |
2.83+-0.24 |
2.94+-0.33* |
Testes (absolute in g) |
3.41+-0.16 |
3.45+-0.18 |
3.42+-0.15 |
3.47+-0.22 |
Epididymides (absolute in g) |
1.18+-0.08 |
1.25+-0.10 |
1.19+-0.10 |
1.23+-0.14 |
Liver (relative) |
2.86+-0.16 |
2.91+-0.22 |
3.14+-0.15** |
3.33+-0.17** |
Kidney (relative) |
0.67+-0.037 |
0.68+-0.046 |
0.71+-0.049 |
0.75+-0.052** |
mean +-SD; *: p<0.05; **: p<0.01 |
x
x
x
Histopathological
findings in the kidney of males treated with neopentyl glycol
Number
of rats with slight (1), moderate (2) or severe (3) effects
Findings |
Dose in mg/kg bw/day |
|||
0 (n=12) |
100 (n=10) |
300 (n=12) |
1000 (n=11) |
|
Basophilic changes |
10 (1) |
9 (1), 1 (2) |
11 (1) |
7 (1), 4 (2) |
Deposits of calcium |
3 (1) |
1 (1) |
1 (1) |
2 (1) |
Eosinophilic body |
12 (1) |
10 (1) |
12 (1) |
11 (1) |
Hyaline droplets |
0 |
1 (1) |
0 |
4 (1) |
Protein casts |
1 (1) |
1 (1) |
2 (1) |
5 (1) |
Lymphocytic infiltration |
0 |
1 (1) |
1 (1) |
0 |
Fibrosis |
0 |
1 (1) |
0 |
0 |
x
x
x
Reproductive
performance in rats treated with neopentyl glycol and
developmental effects in offsprings
Parameter |
Dose in mg/kg bw/day |
|||
0 |
100 |
300 |
1000 |
|
No. of pairs mates |
12 |
12 |
12 |
12 |
Estrus cycle (days) |
4.0+-0.1 |
4.0+-0.1 |
4.1+-0.3 |
4.3+-0.4* |
No. of pairs copulated |
12 |
11 |
12 |
12 |
Copulation index in % |
100 |
92 |
100 |
100 |
No. of pregnant rats |
12 |
10 |
12 |
11 |
Gestation index in % |
92 |
100 |
100 |
100 |
No. of dams delivered live pups |
11 |
10 |
12 |
11 |
Duration of gestation (days) |
21.1+-0.3 |
21.3+-0.5 |
21.3+-0.5 |
21.4+-0.5 |
Fertility index in % |
100 |
91 |
100 |
92 |
No. of corpora lutea per litter |
15.5+-1.0 |
15.7+-1.2 |
16.1+-1.7 |
14.9+-1.8 |
No. of implants per dam |
14.8+-1.2 |
15.2+-1.3 |
15.3+-1.2 |
13.9+-2.7 |
Implantation index in % |
96+-4.6 |
97+-3.4 |
96+-6.2 |
93+-14.0 |
No. of live pups born per litter |
13.7+-1.2 |
14.1+-1.6 |
14.0+-2.8 |
12.8+-2.2 |
Delivery index in % |
93+-5.1 |
93+-7.1 |
91+-15.6 |
93+-5.3 |
Sex ratio (m/f) |
0.80 |
1.17 |
0.98 |
0.88 |
No. of dead pups born per litter |
0.1+-0.3 |
0 |
0 |
0 |
Birth index in % |
93+-6.1 |
93+-7.1 |
91+-15.6 |
93+-5.3 |
No. of live pups per litter at pn day 3 # |
13.3 |
13.7 |
13.8 |
12.5 |
Viability index pn day 4 in % (males) |
97+-6.8 |
100 |
98+-5.3 |
99+-3.8 |
Viability index pn day 4 in % (females) |
96+-7.8 |
95+-8.1 |
99+-2.4 |
97+-6.3 |
Litter weight at birth # |
79.5 |
79.2 |
78.5 |
74.7 |
Litter weight at pn day 3 # |
104 |
103 |
102 |
98 |
Pup weight at birth # |
5.8 |
5.5 |
5.7 |
5.8 |
Pup weight at pn day 3 # |
7.9 |
7.5 |
7.7 |
7.9 |
Dams with pups showing abnormalities (except trauma) |
0/11 |
0/10 |
0/12 |
0/11 |
Dams with no pn loss of offspring |
7 |
7 |
9 |
8 |
Dams with pn loss of offspring |
4 |
3 |
3 |
3 |
Mean +- SD; pn: post natal; #: mean given but not SD; *: p<0.05 |
Copulation index: (no. of dams with successful copulation/no. of rats mated) x 100
Fertility index: (no. of pregnant rats/ no. of rats with successful copulation) x 100
Gestation index: (no. of dams with live pups/ no. of pregnant dams) x 100
Implantation index: (no. of total implants/ no. total corpora lutea) x 100
Delivery index: (no. of pups born/ no. of implants) x 100
Birth index: (no. live pups born/number of implants) x 100
Viability index pn day 4: (no. of live pups at pn day 4/ no. of live pups born) x 100
Applicant's summary and conclusion
- Conclusions:
- Reproductive performance of the parent generation and development of the F1 generation were not affected after oral application of dose levels up to 1000 mg/kg bw/day. Concerning repeated dose toxicity the high dose resulted in no toxic effects in females but in males; the NOAEL is 300 mg/kg bw/day.
- Executive summary:
The study was conducted according to OECD Guideline 422. GLP standards were fulfilled. Since a detailed report in English is not available (only in Japanese with tables in English) not all details of this study are documented but the data base is sufficient for evaluation. Acceptable restrictions: no data were given on historical control range for hematology and clinical chemistry of this laboratory; hematology & clinical chemistry only in males; no details about test animals, application volume and concentration, mating procedure, analysis of dose, and stability in vehicle.
Twelve male and 12 female Sprague-Dawley rats per dose were gavaged with 0, 100, 300, or 1000 mg/kg bw/day. The exposure period for males was 45 days; females were treated from day 14 before mating to day 3 of lactation. The premating exposure period for males was not clearly stated but presumably ca. 6 weeks. There was no post exposure observation period. Body weight and food consumption was measured in all groups. Estrous cyclicity was determined before mating. Hematology and clinical chemistry was performed in males. The following litter observations were recorded: live pups at birth and at day 4 (termination); sex ratio; litter & pup weight at birth and at day 4; loss of offsprings; abnormal pups. At termination organ weights (absolute and relative) were determined and necropsy and histopathology performed. The following reproductive/developmental indices were measured: copulation index, fertility index, gestation index, implantation index, delivery index, birth index, and viability index on day 4.
The reproductive performance and the development of the offspring were not affected by oral application of dose levels up to 1000 mg/kg bw/day. Concerning the repeated dose toxicity in females of the parent generation no effects were detected. At 100 mg/kg bw/day no effects were recorded in males. At >= 300 mg/kg bw/day a dose dependent increases in the levels of total protein, total bilirubin and albumin in clinical chemistry was measured and the absolute and relative liver weight was increased in males. At a dose level of 1000 mg/kg bw/day a reduced blood glucose value was observed and absolute and relative kidney weight was increased in males; histopathology of high dose males revealed hypertrophy of the liver in 2/12 males, increased severity in basophilic alteration of the renal tubular epithelium accompanied by an increased incidence in hyaline droplets and protein casts.
The toxicological relevance of altered parameters in clinical chemistry is questionable. No comparison is available with historical control ranges of the same laboratory. These data are not used for final evaluation. The increase in liver weight was not found to be parallel to any histpathologically detected liver lesion and furthermore no clear indication of such a liver lesion was found in other parameters investigated. Therefore, the increase in liver weight at mid and high dose level and liver hypertrophy at the high dose is considered to be an adaption to the increased metabolism of neopentyl glycol and not an adverse effect per se. However, the increased kidney weight at 1000 mg/kg bw/day accompanied by hyaline droplets and protein casts in the eliminating renal lumen plus alterations of the renal tubular epithelium (increased basophilicity) are suggested to be adverse in nature.
Conclusion: Reproductive performance of the parent generation and development of the F1 generation were not affected after oral application of dose levels up to 1000 mg/kg bw/day. Concerning repeated dose toxicity the high dose resulted in no toxic effects in females but in males; the NOAEL is 300 mg/kg bw/day.
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