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Diss Factsheets

Administrative data

reproductive toxicity, other
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
Not reported
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
see section 13 in IUCLID for read-across justification report
Reason / purpose for cross-reference:
reference to same study

Data source

Reference Type:
The reproductive and developmental toxicity of indium in the Swiss mouse
Chapin RE, Harris MW, Hunter ES, Davis BJ, Collins BJ and Lockhart AC
Bibliographic source:
Fundam Appl Toxicol. 27(1):140-148.

Materials and methods

Test guideline
no guideline followed
Principles of method if other than guideline:
Short-term reproductive toxicity screen. Female Swiss mice (group 1) were dosed for 20 days (study days 1-20) by gavage to 0, 50, 150 or 250 mg/kg/d InCl3. Males (group 3) were dosed for 17 days (study days 3-20) by gavage to 0, 50, 150 or 250 mg/kg/d. Males and females were cohabited and mated on study days 7-11.
GLP compliance:
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Indium trichloride
EC Number:
EC Name:
Indium trichloride
Cas Number:
Molecular formula:
indium trichloride
Details on test material:
- Name of test material (as cited in study report): indium trichloride
- Analytical purity: 99.9+%

Test animals

Details on test animals or test system and environmental conditions:
- Source: Charles River Labs (Raleigh, NC)
- Age at study initiation: (P) 55-65 days
- Weight at study initiation: (P) 27-31g
- Housing: polycarbonate shoebox cages with harwood bedding (BetaChips, Northeastern Products Corp, Warrensburg, NY)
- Diet (ad libitum): NIH-07 feed
- Water (ad libitum): deionized water
- Acclimation period: 10-14 days

- Temperature (°C): 20 ± 1°C
- Humidity (%): 50 ± 10%

Administration / exposure

Route of administration:
oral: gavage
Details on exposure:
The test substance was dissolved in water at concentrations between 5 and 35mg/ml and administred to adult male and female Swiss mice daily by oral gavage.
Details on mating procedure:
- M/F ratio per cage: 1:1 or 1:2
- Length of cohabitation: Males and females were cohabited and mated on study days 7-11
- Proof of pregnancy: Sperm in vaginal smear or plug during cohabitation

Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
-males (group 3): dosed from study day 3 until study day 20
-females (group 1): continuously exposed: day 0 until day 20
-females (group 2): gestational exposure: day 8 until day 14
Frequency of treatment:
Details on study schedule:
Males (group 3) are, prior to chemical exposure, cohabited with a group of females (group2) for the first 3 days of the study. The animals are separated at the end of cohabitation. The females are housed until they are dosed from gestation day 6-15. They are allowed to give birth, and rear their young until postnatal day 4. Meanwhile, the males are dosed from study day 3 until 20. These males are again mated with another group of females (group1) from study day 7 until 11. During this time, both sexes are treated with the compound.

Doses / concentrationsopen allclose all
Dose / conc.:
50 mg/kg bw/day
Dose / conc.:
150 mg/kg bw/day
Dose / conc.:
250 mg/kg bw/day
No. of animals per sex per dose:
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale:
A 22-day dose-range-finding (DRF) study was conducted to set doses for the main study. This DRF study involved no mating, just dosing to group-housed adult rats. Doses tested were: 50, 150, 250 and 350 mg/kg/d.
Positive control:


Parental animals: Observations and examinations:
- Time schedule for examinations: group 1 females: day 0,4,12,16,20,21; group 3 males: day 3,7,11,15,19,21; group 2 females: gestation day 0, 8, 12, 15 and post natal day 1, 4
Oestrous cyclicity (parental animals):
Number of live/dead implants
Total implants/corpora lutea

Sperm parameters (parental animals):
Parameters examined in male parents:
Epididymal sperm motility and total epididymal sperm count
Litter observations:
The following parameters were examined in F1 offspring:
Number of pups, stillbirths, live births, postnatal mortality, weight gain
Postmortem examinations (parental animals):
- Male animals: All surviving animals at day 21
- Maternal animals: All surviving animals after postnatal day 4
HISTOPATHOLOGY / ORGAN WEIGHTS: on liver, kidney, testis
Postmortem examinations (offspring):
No data
Initial and terminal body weights, body weight changes, absolute and relative organ weights, and conceptus and pup data were analyzed to detect dose-related trends using Jonckheere's test against ordered alternatives followed by the Mann-Whithney U test for pairwise comparisons. An exact permutation test was used to detect dose-related trends in fertility rates and neonatal deaths.
Reproductive indices:
Offspring viability indices:

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Details on results (P0)

group 1 (males): dose related decrease in body weight gain, with the high dose animals losing weight during the study. Food consumption is reduced during the first 11 days of exposure only in the high dose group
group 2 (females- continuously exposed): animals in the top dose group consumed slightly less food than controls and gained less than half the weight that controls gained during the course of the study
group 3 (females -gestational exposure): females dosed during fetal organogenesis with the high dose level consumed less food than controls, and animals in the middle dose group consumed less food from gestational day 8-12. There was a dose-related inhibition of weight gain that started at the lowest dose group, and animals in both middle and high dose groups gained significantly less weight during the experiment and finished lighter than controls.

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS): no change in any fertility endpoint (number of live implants, number of dead implants, number of resorptions, number of corpora lutea

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS): no effects on sperm parameters, fertility before and during chemical administration (group 1 males)


ORGAN WEIGHTS (PARENTAL ANIMALS): no effects on organ weights (group 1 males)

HISTOPATHOLOGY (PARENTAL ANIMALS): No changes in the structure of kidneys or livers (known target organs of cadmium toxicity) (sytemic toxicity only evaluated in males)

OTHER FINDINGS (PARENTAL ANIMALS): eosinophils were reduced at the high dose group. Serum enzymes indicative of liver damage were slightly increased in the high dose group. Serum albumin levels were increased slightly; no increase in Cd-U or in protein levels

Effect levels (P0)

Dose descriptor:
Effect level:
250 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
reproductive function (oestrous cycle)
reproductive function (sperm measures)
reproductive performance

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Details on results (F1)

VIABILITY (OFFSPRING): there was an increase in fetal death (dead pups at birth) at the highes dose (250mg/kg/d)
BODY WEIGHT (OFFSPRING): live-born high-dose pups weighted less than controls at birth and on PND1

Effect levels (F1)

Dose descriptor:
Based on:
test mat.
Basis for effect level:
other: overall effects: viability: there was an increase in fetal death (dead pups at birth) at the highest dose (250mg/kg/d) body weight: live-born high-dose pups weighted less than controls at birth and on PND1
Remarks on result:
not measured/tested

Overall reproductive toxicity

Reproductive effects observed:

Any other information on results incl. tables


Applicant's summary and conclusion

No evidence of reproductive performance toxicity in the presence of adult systemic toxicity. InCl3 dosed orally up to 250mg/kg/d had no effect on the reproductive performance of either male or female animals.
Overall the available data indicate that InCl3 is not classifiable as a reproductive toxicant
Executive summary:

A sub chronic toxicity and male / female fertility study conducted in Swiss mice designed to assess the effects of indium chloride on male and female gametogenesis, female cyclicity, fertilization and implantation. Female Swiss mice (10 per group) were dosed for 20 days (study days 1-20) by gavage to 0, 50, 150 or 250 mg/kg/d InCl3. Males (10 per group) were dosed for 17 days (study days 3-20) by gavage to 0, 50, 150 or 250 mg/kg/d. Males and females were cohabited and mated on study days 7-11. Systemic toxicity results showed a functional renal effect and a reduction in circulating lymphocyte number in adult males (high dose) and a significant reduction in adult male and female bodyweight (all doses). These effects occurred in the absence of effects on microscopic structure of selected male tissues (including right testis and epididymis), male reproductive parameters (sperm motility assessment and fertility before and during chemical administration) or female fertility endpoints (percentage pregnant, number of live and dead implants, number of corpora lutea and number of uterine implant sites at necropsy). The study demonstrated no effect of indium chloride on male of female fertility and reproductive performance (ability to deliver any young).