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EC number: 204-171-4 | CAS number: 117-08-8
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 982
- Report date:
- 1982
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Tetrachlorophthalic anhydride
- EC Number:
- 204-171-4
- EC Name:
- Tetrachlorophthalic anhydride
- Cas Number:
- 117-08-8
- Molecular formula:
- C8Cl4O3
- IUPAC Name:
- tetrachloro-1,3-dihydro-2-benzofuran-1,3-dione
- Details on test material:
- - Name of test material (as cited in study report): Tetrachlorophthalic anhydride
- Physical state: white solid flake
- Analytical purity: 98.5%
- Stability under test conditions: At least two years from date of manufacture (Lot DA-60 manufactured April 2, 1981)
- Storage condition of test material: closed container at room temperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: females 60 days old (sexually mature, virgin); males (sexually mature)
- Housing: single
- Diet (e.g. ad libitum): Purina Rat Chow 5002
- Water (e.g. ad libitum): tap water
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Appropriate amounts of test article were suspended in corn oil. The test material / corn oil suspensions were prepared fresh weekly. When not in use, dosing suspensions were refrigerated. In formulating dosing suspensions, the amount of test material added was corrected for active ingredient. Animals were dosed at a constant volume of 10 ml/kg bw.
- Analytical verification of doses or concentrations:
- yes
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:2
- Length of cohabitation: one night
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- day 6 to 19 of gestation
- Frequency of treatment:
- daily
- Duration of test:
- 20 days
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 250, 1000, and 2000 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 24
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: A pilot study was conducted to evaluate the toxicity of the test substance in the pregnant rat. Test material was administered by gastric intubation in corn oil to mated female rats (5/ group) during 6-19 gestation interval. Dose levels were 0, 250, 500, 1000, 1750 and 2500 mg/kg bw/day. Females were sacrificed on day 20 of gestation and uterine implantation data evaluated. Accidental death of 1 rat in the 1000 mg/kg bw dose group and 2 rats in the 2500 mg/kg bw dose group occurred during the study. No clear dose-related effect of treatment on mean body weight change during day 6-20 of gestation interval was evident. Physical evaluation revealed yellowish staining of the fur in the ano-genital region and soft stool in several females at the higher dose levels (1750 and 2500 mg/kg bw). No treatment effects were evident in regards to uterine implantation data or maternal gross postmortem findings. Fetal evaluation indicated a slight but consistent reduction in mean weight (both sexes) at the 2500 mg/kg bw dose level. External evaluation recovered at all treated levels did not reveal an increase in malformations.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: days 0, 6, 10, 15 and 20 of gestation
BODY WEIGHT: Yes
- Time schedule for examinations: says 0, 6, 15 and 20 of gestation
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: reproductive system
- Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: [all per litter ]
- Soft tissue examinations: Yes: [half per litter ]
- Skeletal examinations: Yes: [half per litter ] - Statistics:
- For interval data (body wts, wt changes, reproductive data) -Bartlett's test was used to determine equality of variance and ANOVA and Dunnett's test used for parametric data while the Kruskal-Wallis test and Summed Rank test (Dunn) was used for nonparametric data (Snedecor and Cochran.; Hollander and Wolfe). For Incidence data i.e. mortality rates, % and incidence of variations and malformations -comparisons were made using the Chi-square contingency table and the 2x 2 Fisher Exact test using the Bonferroni inequality estimate; linear trend was evaluated using the Armitage test. Comparisons were made using the litter as the comparative entity. Both the 5% and 10% level of statistical significance were reported for each parameter.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Details on maternal toxic effects:
Mortality: One female in each of the low and mid dosage groups and two females in the high dosage group died during the study, but were considered dosing error and not toxicity-related.
Clinical observation: Physical observations recorded included a lethargic appearance in several mid and high-dosage animals and pale eye color on day 20 of gestation in 4 rats in the 2000 mg/kg bw dose group.
Body weight: Mean body weight gains in animals treated with the test article were comparable to controls.
Pregnancy rate: Pregnancy rates for the control, low-, mid- and high-dose groups were 95.8 % (23/24), 91.7 % (22/24), 100 % (24/24) and 95.8 % (23/24), respectively.
Corpora Lutea and Uterine Implantation Data: mean numbers of corpora lutea and implantations sites were similar to control values. The mean number of resorption sites and the mean percentage of resorptions to implants were considered comparable between control and treated groups. The mean number of live fetuses and the mean percentage of live fetuses to implants were comparable between the control and treated groups.
Postmortem examination: No treatment-related gross pathologic findings were seen at autopsy.
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Details on embryotoxic / teratogenic effects:
Fetal body weight: Mean fetal weights (both sexes) were considered comparable between the control, low- and mid- dose groups. Fetal body weights in the high dose group were significantly depressed in male (- 7%) and female (-8 %) pups when compared to controls. No treatment related effects were evident in fetal sexing data.
Ossification Variation: The types and incidences of ossification variations were comparable between the low, mid and control groups. In the high dose group, a slight increase in the incidence of asymetric/unossified sternebra and incompletely ossified thoracic vertebral centra were observed and are considered representative of a fetotoxic effect.
Fetal external and soft tissue examination: The incidence of external and soft tissue anomalies among treated groups was similar to controls both on a per fetus and per litter basis.
Fetal skeletal examination: The incidence of skeletal malformations was comparable between the control, low and mid dosage groups. The incidence of fetuses with skeletal malformations and the incidence of litters containing an affected fetus for the high-dose group were higher than control, however these differences were not statistically significant. Rib malformations, exclusive of wavy ribs were seen in 3 of the 153 high dose fetuses (an incidence of 2 %). No similar rib malformations were seen in the 159 control, 150 low-dose and 154 mid-dose fetuses evaluated. Total incidence for the control, low, mid and high dose groups were 1.9%, 1.3, 1.3 and 4.6%, respectively.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Summary of malformation data
Dose groups (mg/kg bw) |
Malformation |
Fetuses |
Litters |
||
No.a |
% |
No.b |
% |
||
0 |
Wavy ribs (bilateral) |
3/159 |
1.9 |
1/23 |
4.3 |
250 |
Wavy ribs - alone |
1/150 |
0.7 |
1/21 |
4.8 |
Wavy ribs - with angulated ribs |
1/150 |
0.7 |
1/21 |
4.8 |
|
Total |
2/150 |
1.3 |
2/21 |
9.5 |
|
1000 |
Hindlimb- digits shortened (unilateral) |
1/154 |
0.6 |
1/22 |
4.5 |
Cervical vertebral defect |
1/154 |
0.6 |
1/22 |
4.5 |
|
Total |
2/154 |
1.3 |
2/22 |
9.1 |
|
2000 |
Wavy ribs (bilateral) |
2/153 |
1.3 |
2/21 |
9.5 |
Fused ribs and vertebral defect |
1/153 |
0.7 |
1/21 |
4.8 |
|
Vertebral defects – fused vertebral transverse processes |
1/153 |
0.7 |
1/21 |
4.8 |
|
Cervical vertebral transverse process fused to exoccipital |
1/153 |
0.7 |
1/21 |
4.8 |
|
Additional rib-like structures |
2/153 |
1.3 |
1/21 |
4.8 |
|
Totalc |
7/153 |
4.6 |
5/21 |
23.8 |
No statistically significant differences from control.
aNo. of fetuses with a malformation/No. of fetuses examined per group
bNo. of litters containing fetuses with a malformation/ No. of litters evaluated.
cThe total number of litters containing affected fetuses may not represent the sum of litters containing fetuses with individual malformations in that some litters contained more than one malformed fetus.
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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