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EC number: 204-485-1 | CAS number: 121-60-8
- 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:
- weight of evidence
- Reliability:
- 4 (not assignable)
Data source
Referenceopen allclose all
- Reference Type:
- other: study report
- Title:
- Unnamed
- Year:
- 2 003
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD TG No. 422 “Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test
- Principles of method if other than guideline:
- According to OECD TG No. 422 “Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test
- GLP compliance:
- not specified
Test material
- Reference substance name:
- 4-Methylbenzenesulfonyl chloride
- Cas Number:
- 98-59-9
- Molecular formula:
- C7H7ClO2S
- IUPAC Name:
- 4-Methylbenzenesulfonyl chloride
- Test material form:
- not specified
- Details on test material:
- Name: p-Toluenesulfonyl chloride
CAS No.: 98-59-9
Molecular Formula: C7-H7-Cl-O2-S
Molecular Weight: 190.6493 g/mol
SMILES: Cc1ccc(cc1)S(=O)(=O)Cl
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation:9 weeks old
- Weight at study initiation: - 363.1 g for males and 198.5 - 229.3 g for females
Administration / exposure
- Route of administration:
- oral: gavage
- Type of inhalation exposure (if applicable):
- not specified
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- No Data Available
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No Data Available
- Details on mating procedure:
- No Data Available
- Duration of treatment / exposure:
- 34, 36 - 45, and 51 days for male, copulated female and not copulated female animal
- Frequency of treatment:
- Daily
- Duration of test:
- 34-51, covering the full duration of pregnancy
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 150, 350 and 750 mg/kg/day
Basis:
- No. of animals per sex per dose:
- 60 animals for each sex
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- No Data Available
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule:daily
- Cage side observations checked in table [No.?] were included.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:Weekly
BODY WEIGHT: Yes
- Time schedule for examinations:once a week and just before the necropsy, but in case of pregnant females, it was measured on the day 0, 7, 14, 20 of the gestation period, date of delivery, and 4 days of the lactation day
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
once a week except mating period
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
POST-MORTEM EXAMINATIONS: Yes / No / No data
- Sacrifice on gestation day #
- Organs examined:
OTHER: - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: - Fetal examinations:
- There were no abnormalities in the treatment groups but in the control groups, a case
of runt and 2 cases of blunt-tipped tail were observed. On the day 4 of lactation, 2 cases of blunt-tipped tail were observed but no abnormalities in the treatment groups - Statistics:
- Statistical decision tree, but in case of recovery group, either two-side Student’s t-test or two-side Aspin-Welch t-test was used. In case of categorical data, two-sided Fisher’s exact test was used
- Indices:
- Reproductive indices:
- Copulation index
- number of implantations
- number of corpus luteum
- Number of females pregnant
Offspring viability indices:
- Number of life pups
- post natal loss
- pre and post-implantation loss - Historical control data:
- Tissues were fixed to do histopathologic tests such
as testes, epididymides, ovaries, accessory sex organs for all animals,
brain (including cerebrum, cerebellum and pons), spinal cord, stomach,
small and large intestines (including peyer’s patches), liver, kidneys,
adrenals, spleen, heart, thymus, thyroid, trachea, lungs, uterus, urinary
bladder, lymph nodes (cervical mesenteric), peripheral nerve (sciatic or
tibial), bone marrow
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- 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:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Other effects:
- not specified
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
CLINICAL SIGNS AND MORTALITY
No mortality males; in females 350 mg/kg: 2/12 and at 750 mg/kg: 4/18
In the control groups, there were no specific clinical symptoms during test period.
150 mg: Intermittent (blood-like) salivation and staining around mouth (3/18 males, 6/18 females), and in females at delivery: difficult delivery, poor nursing, irregular respiration, uterus introsusception and piloerection.
350 mg: Intermittent (blood-like) salivation and staining around mouth were observed after day 15 and (blood-like) staining around nose (7/12 males, 4/12 females). Iintermittent soft stool and staining around anorectal region were observed for the most male animals and in 2 females. One female showed difficult delivery, lacrimation, and irregular respiration from day 4.
750 mg: soft stool and staining around anorectal region for most males and all females; and 5 cases of loss of hair around tail region were observed. Intermittent (blood-like) salivation and 9 cases of staining around mouth and 9 cases of (blood-like) staining around nose. Soft stool and staining around anorectal region for all animals; some cases of intermittent diarrhea were observed. Some animals with found dead and in dying condition had symptoms such as irregular respiration, crawing position, hypoactivity, and abdominal swelling.
In the 750 mg/kg/day recovery group, salivation, staining around mouth, soft stool and staining around anorectal region were not observed during the recovery period.
BODY WEIGHT AND WEIGHT GAIN
From start of dosing BW gain at 750 mg/kg group a bit lower resulting to a lower BW of 8% in males and 5.5% in females compared to controls during first week of recovery which partly recovered during the second week of the recovery period.
FOOD CONSUMPTION:
Only during the first week food consumption some somewhat lower in the 750 mg group.
HAEMATOLOGY
No major changes were seen compared to control, although the reported that dose related decrease in RBC and HCT and an increase in platelet counts were observed in males.
CLINICAL CHEMISTRY
In males and females BUN is decreased compared to control at 750 mg/kg but not in the recovery groups. Total cholesterol was decreased in the recovery groups. In females chloride is decreased at 750 mg/kg.
NEUROBEHAVIOUR
No significant effects were found.
ORGAN WEIGHTS
No effects were seen in sex-organ weights. Weight of the spleen was increased in treatment groups compared to controls for both males and females, although in females not relative weight. No differences in spleen weights were seen in recovery groups. In males the absolute, but not the relative, weight of the heart was decreased in the 750 mg/kg group. In the female recovery group the weights for adrenal and the brain were increased.
GROSS PATHOLOGY
No information provided.
HISTOPATHOLOGY:
dose related effects of epithelial proliferation and inflammation of the forestomach already visible in animals treated at 150 mg
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 750 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Remarks on result:
- other: not specified
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- not specified
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
Number of pups born, viability and sex ratio: No significant difference was observed between the treatment groups and the control group at the time of the delivery and on the day 4 of the lactation.
External examination of pups (group) showed no developmental abnormalities
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 750 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reduction in number of live offspring
- changes in sex ratio
- fetal/pup body weight changes
- changes in litter size and weights
- changes in postnatal survival
- external malformations
- skeletal malformations
- visceral malformations
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Fetal abnormalities
- Abnormalities:
- not specified
- Localisation:
- other: not specified
- Description (incidence and severity):
- not specified
Overall developmental toxicity
- Developmental effects observed:
- no
- Treatment related:
- no
Any other information on results incl. tables
Body weights of pups (group)
Group |
Sex |
Pup BW at birth |
At lactation day 4 |
||
Male |
Female |
Male |
Female |
||
0 |
Mean |
6.25 |
5.75 |
8.57 |
8.03 |
SD |
0.6 |
0.66 |
1.26 |
1.18 |
|
N |
67 |
69 |
66 |
69 |
|
150 |
Mean |
5.99 |
5.62 |
8.56 |
7.98 |
SD |
0.56 |
0.46 |
1.34 |
1.27 |
|
N |
62 |
70 |
63 |
66 |
|
350 |
Mean |
6.37 |
5.73 |
9.71 |
8.59 |
SD |
0.9 |
0.8 |
2.17 |
1.57 |
|
N |
59 |
48 |
55 |
44 |
|
750 |
Mean |
5.98 |
5.59 |
8.7 |
8.21 |
SD |
0.6 |
0.51 |
0.87 |
0.74 |
|
N |
48 |
51 |
46 |
49 |
External examination of pups (group)
Group |
No. |
At birth |
No. |
Lactation day 4 |
||||
No.of pups examined |
No.of pups |
Obser-vations |
No.of pups examined |
No.of pups |
Obser-vations |
|||
0 |
11 |
143 |
140 |
NGF |
11 |
136 |
134 |
NGF |
|
|
|
2 |
BT |
|
|
2 |
BT |
|
|
|
1 |
Runt |
|
|
|
|
150 |
11 |
143 |
144 |
NGF |
11 |
129 |
129 |
NGF |
350 |
10 |
116 |
116 |
NGF |
9 |
100 |
100 |
NGF |
750 |
9 |
105 |
105 |
NGF |
8 |
95 |
95 |
NGF |
NGF: No Gross findings
BT: Blunt-tipped Tail
Applicant's summary and conclusion
- Conclusions:
- The No observed adversed effect level NOAEL value of 4-Methylbenzenesulfonyl chloride on rat was observed at a dose level of 750 mg/kg/day.
- Executive summary:
The toxicity of Tosyl chloride has been evaluated in a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test according to OECD 422 and in compliance to GLP. Tosyl chloride was dose by gavage to groups of 12 Sprague-Dawley rats/sex/dose level at levels of 0, 150, 350 and 750 mg/kg/day for 35 days and 36 - 51 days for male and female rats, respectively. A separate group of 6 animals/sex were added for a 14-day recovery group to the control and the high dose groups. No mortality males; in females 350 mg/kg: 2/12 and at 750 mg/kg: 4/18. Some clinical signs were observed at the dose level of 150 mg/kg/day in both male and females such as intermittent (blood-like) salivation and staining around mouth. Effects were more severe at 350 mg/kg and at 750 mg/kg reported clinical signs were soft stool and staining around anorectal region for most males and all females; and 5 cases of loss of hair around tail region were observed. Intermittent (blood-like) salivation and 9 cases of staining around mouth and 9 cases of (blood-like) staining around nose. Soft stool and staining around anorectal region for all animals; some cases of intermittent diarrhea were observed. A decreased BW gain was observed in the 750 mg group resulting to a lower BW that was maximal 8% lower in males and 5.5% in females compared to controls. Food consumption was a bit lower during the first week in the 750 mg group. Histopathology showed dose related effects of epithelial proliferation and inflammation of the forestomach already visible in animals treated at 150 mg.In the 750 mg/kg/day recovery group, salivation, staining around mouth, soft stool and staining around anorectal region were not observed during the recovery period.
Thus from above findings we can conclude that NOAEL for developmental effects was stated to be above the highest tested dose (750 mg/kg/day)
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