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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

C(M)IT/MIT was tested in one 1-generation reproductive toxicity study and one 2-generation reproductive toxicity study in rats.

Link to relevant study records

Referenceopen allclose all

Endpoint:
two-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 83-4 (Reproduction and Fertility Effects)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Directive 87/302/EEC Part B
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japan 59 Nohsan No. 4200
Deviations:
no
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Rohm and Haas, Batch No. 0157A001

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Soluble and stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dilution in water
- Final dilution of a dissolved solid, stock liquid or gel: 30, 100, 300 ppm a.i.

OTHER SPECIFICS: Purity of test material was 14.8%
Species:
rat
Strain:
other: Crl:CD BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Hollister, California, USA
- Age at study initiation: (P) 6-7 wks; (F1) 3 wks
- Weight at study initiation: (P) Males: 240-290 g; Females: 170-195 g
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Prepared fresh once per week by diluting the test material with water
Details on mating procedure:
- M/F ratio per cage: 1 to 1
- Length of cohabitation: 2 weeks
- Proof of pregnancy: vaginal plug or sperm in vaginal smear, referred to as day 0 of pregnancy
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analytical results of the dosing solutions confirmed that the water preparation procedure provided homogeneous mixtures of the test substance in water, the Kathon™ 886F biocide concentrations ranged from 90-105 % of nominal target concentrations at all levels, and Kathon™ 885F biocide is stable in water for at least 14 days at room temperature.
Duration of treatment / exposure:
10 weeks
Frequency of treatment:
Continuous, drinking water with test substance was renewed weekly
Details on study schedule:
- Selection of parents from F1 generation when pups were 21 days of age.
- Age at mating of the mated animals in the study: 6-7 weeks
Dose / conc.:
30 ppm (nominal)
Remarks:
Based on a.i.
Dose / conc.:
100 ppm (nominal)
Remarks:
Based on a.i.
Dose / conc.:
300 ppm (nominal)
Remarks:
Based on a.i.
No. of animals per sex per dose:
26/sex/group
Control animals:
yes, concurrent no treatment
other: water with inorganic salt (stabilizer) content of highest dose
Details on study design:
- Rationale for animal assignment (if not random): Animals were assigned to dose groups using a computerized randomisation procedure based on body weight.
Positive control:
n/a
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly for male and female animals until cohabitation. Females weighed on Days 0,7, 14 and 21 of gestation, and Days 0,4,7, 14 and 21 of lactation. Determined every four weeks after cohabitation for unmated females and males for health monitoring purposes.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Weekly for male and female animals until cohabitation. During gestation, feed consumption was measured from Days 0-7, 7-14 and 14-2 1. Feed consumption was only measured during lactation from Days 0-7 and 7-14 due to the pups interfering with consumption from Days 14-21.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Weekly for male and female animals until cohabitation. During gestation, water consumption was measured from Days 0-7, 7-14 and 14-2 1. Water consumption was only measured during lactation from Days 0-7 and 7-14 due to the pups interfering with consumption from Days 14-21.
Oestrous cyclicity (parental animals):
During the three weeks immediately prior to mating, estrus cycling was evaluated in all P1 and P2 females by examination of cytology in daily vaginal lavage samples. This examination continued during cohabitation until positive evidence of mating was noted.
Sperm parameters (parental animals):
Parameters examined in P and F1 male parental generations:
sperm count in testes, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm motility, sperm morphology.
Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of 8 pups/litter (4/sex/litter were possible); excess pups were killed and discarded.

PARAMETERS EXAMINED
The following parameters were examined in F1 and F2 offspring:
number and sex of pups, stillbirths, live births, presence of gross anomalies, weight gain, physical or behavioural abnormalities

GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead.
Postmortem examinations (parental animals):
SACRIFICE
- Maternal animals: All surviving animals after the last litter of each generation was weaned.

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.

HISTOPATHOLOGY / ORGAN WEIGHTS
- Organ weights: adrenals, brain, kidneys, liver, spleen, thymus, ovary, uterus, testes, single epididymis (total and cauda), seminal vesicles (with coagulating glands and their fluids) and prostate.
- Tissues saved and fixed: adrenals, brain, kidneys, liver, pituitary, spleen, thymus, gross lesions, ovary, oviducts in females, uterus with cervix, testes, epididymis, seminal vesicles (with coagulating glands), prostate and stomach.
Postmortem examinations (offspring):
SACRIFICE
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the thoracic and abdominal viscera.

HISTOPATHOLOGY / ORGAN WEIGTHS
- Organ weights: brain, spleen, thymus on one pup/sex/litter at weaning post natal day 21.
- Microscopic examination of the stomach
Statistics:
The litter (i.e., proportion of pups/litter, or litter mean) was used, where appropriate, as the experimental unit for the purpose of statistical evaluation. ANOVA and Fisher's Exact test were used to analyze the parameters studied. The level of statistical significance selected was p<0.05.
Reproductive indices:
Gestation index, mating index, fertility index.
Offspring viability indices:
Viability index, lactation index.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Males exposed to 300 ppm showed a treatment-related decrease (5 %) in mean body weight during weeks 1 through 6 of treatment.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Males exposed to 300 ppm showed a treatment-related decrease (5 %) in mean body weight during weeks 1 through 6 of treatment.
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
Treatment-related and concentration-dependent decreases in water consumption were noted in all-Kathon™ exposed groups through most of the premating, gestation and lactation periods.
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Other effects:
effects observed, treatment-related
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
TEST SUBSTANCE INTAKE (PARENTAL ANIMALS)
Treatment-related and concentration-dependent decreases in water consumption were noted in all-Kathon™ exposed groups in both the P1 and P2 animals through most of the premating, gestation and lactation periods.

HISTOPATHOLOGY (PARENTAL ANIMALS)
Treatment-related microscopic findings were limited to the stomach of male and female parental animals at 100 and/or 300 ppm. These changes included an increased incidence of focal superficial erosions of the glandular mucosa, edema and inflammation of the submucosa of the glandular and nonglandular areas, and hyperplasia and hyperkeratosis of the nonglandular stomach.
Key result
Dose descriptor:
NOAEL
Effect level:
30 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: overall effects
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
Treatment-related and concentration-dependent decreases in water consumption were noted in all-Kathon™ exposed groups through most of the premating, gestation and lactation periods.
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Treatment-related microscopic findings were limited to the stomach of male and female parental animals at 100 and/or 300 ppm. These changes included an increased incidence of focal superficial erosions of the glandular mucosa, edema and inflammation of the submucosa of the glandular and nonglandular areas, and hyperplasia and hyperkeratosis of the nonglandular stomach.
Histopathological findings: neoplastic:
not specified
Other effects:
not examined
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
30 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
body weight and weight gain
histopathology: non-neoplastic
Key result
Dose descriptor:
NOAEL
Effect level:
300 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
reproductive function (oestrous cycle)
reproductive function (sperm measures)
reproductive performance
Remarks on result:
not determinable due to absence of adverse toxic effects
Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Other effects:
not examined
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
Dose descriptor:
NOEL
Generation:
F1
Effect level:
300 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: reproduction and development
Remarks on result:
not determinable due to absence of adverse toxic effects
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Other effects:
not examined
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
Key result
Dose descriptor:
NOAEL
Generation:
F2
Effect level:
300 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
viability
clinical signs
histopathology: non-neoplastic
Key result
Reproductive effects observed:
no
Conclusions:
Rats exposed to Kathon™ 886F biocide in the drinking water for two generations had a NOAEL for parental animal toxicity of 30 ppm (2.8-4.4 mg/kg/day in the P1 animals and 4.3-5.5 mg/kg/day in the P2 animals). The reproductive and developmental NOEL was 300 ppm (22.7-28.0 mg/kg/day in the P1 animals and 35.7-39.1 mg/kg/day in the P2 animals).
Executive summary:

Kathon™biocide: two-generation reproductive toxicity study in rats. No treatment-related deaths or clinical signs of systemic toxicity in either sex up to and including 300 ppm. No treatment-related effects on body weights up to and including 100 ppm in males and females and 300 ppm in females. In 300 ppm males, a treatment-related decrease (5 %) in mean body weight was seen during weeks 1 through 6 of treatment. No treatment-related effects on premating feed consumption in either sex at any dose level. Treatment-related and concentration-dependent decreases in water consumption were noted in all-Kathon™ exposed groups in both the P1 and P2 animals through most of the premating, gestation and lactation periods. No treatment-related effects on any endpoint of mating or fertility in either generation at any dose level. No treatment related effects on sperm motility, testicular sperm count or caudal epididymal reserves of P1 and P2 males at any dose level. Treatment-related microscopic findings were limited to the stomach of male and female parental animals at 100 and/or 300 ppm. These changes included an increased incidence of focal superficial erosions of the glandular mucosa, edema and inflammation of the submucosa of the glandular and nonglandular areas, and hyperplasia and hyperkeratosis of the nonglandular stomach. Rats exposed to Kathon™ 886F biocide in the drinking water for two generations had a NOAEL for parental animal toxicity of 30 ppm (2.8-4.4 mg/kg/day in the P1 animals and 4.3-5.5 mg/kg/day in the P2 animals). The reproductive and developmental NOEL was 300 ppm (22.7-28.0 mg/kg/day in the P1 animals and 35.7-39.1 mg/kg/day in the P2 animals).

Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
Deviations:
yes
Remarks:
Only 10 females were mated and allowed to deliver rather than the suggested 20 females described in OECD 415
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Rohm and Haas, Batch No. SW 81-0138

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Soluble and stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dilution in tap water
- Final dilution of a dissolved solid, stock liquid or gel: 25, 75, 225 ppm a.i., equivalent to 3, 8 and 20 mg a.i./kg

OTHER SPECIFICS: Purity of test material was 15.5%
Species:
rat
Strain:
other: COBS-CD(SD)Br
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Kingston Facility, Kingston, New York, USA.
- Age at study initiation: (P) 6 wks
- Weight at study initiation: (P) Males: 177-221 g; Females: 122-157 g
- Fasting period before study: Not described
- Housing: Not described
- Diet (e.g. ad libitum): Not described
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not described
Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Prepared by diluting test material in tap water. Solutions were prepared fresh weekly.
Details on mating procedure:
- Length of cohabitation: 5 days
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy
- After 5 days of unsuccessful pairing replacement of first male by another male with proven fertility.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Not described
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Daily
Dose / conc.:
25 ppm
Remarks:
Nominal a.i. in water
Dose / conc.:
75 ppm
Remarks:
Nominal a.i. in water
Dose / conc.:
225 ppm
Remarks:
Nominal a.i. in water
No. of animals per sex per dose:
10 males and 10 females/group
Control animals:
yes, concurrent vehicle
other: Same inorganic ion concentration as the high dose group
Positive control:
n/a
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily

BODY WEIGHT: Yes
- Time schedule for examinations:
Males and females were dosed for 15 weeks and weighed weekly prior to the reproductive phase of the study.
Pregnant dams were weighed on days 0, 6, 15 and 20 of gestation and days 0, 4, 7, 14 and 21 of lactation.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Weekly beginning one week prior to study initiation.
Oestrous cyclicity (parental animals):
Gonads were microscopically examined at the end of 13 weeks of dosing.
Sperm parameters (parental animals):
Parameters examined in P male parental generations: not described
other: not described
Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities

GROSS EXAMINATION OF DEAD PUPS:
yes, for presence of milk in their stomachs
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: All surviving animals at the end of the mating period
- Maternal animals: All surviving animals at day 21 lactation

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.

HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table 1 were prepared for microscopic examination and weighed, respectively.
Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring were sacrificed at 21 days of age.

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the thoracic and abdominal viscera.

HISTOPATHOLOGY / ORGAN WEIGTHS
Not described
Statistics:
Body weight, food consumption, and organ weight data were analyzed using Student's "t" test. Water consumption, clinical chemistry, and hematology data were analyzed by an analysis of variance and Duncan's multiple range test. Where suspected differences existed in the reproductive data, these were analyzed by a generalized Wilcoxon test.
Reproductive indices:
Not described
Offspring viability indices:
Not described
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Dams at the high concentration (225 ppm a.i.) showed a significantly decreased body weight on lactation day 21
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Dams at the high concentration (225 ppm a.i.) showed a significantly decreased body weight on lactation day 21
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
Dams at the high concentration (225 ppm a.i.) showed a significant decrease in water consumption during weeks 2 and 3 of gestation and for the first week of lactation.
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
Key result
Dose descriptor:
NOEL
Effect level:
225 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: overall effects
Dose descriptor:
NOAEL
Effect level:
24.7 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
female
Basis for effect level:
other: overall effects
Dose descriptor:
NOAEL
Effect level:
16.3 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: overall effects
Key result
Critical effects observed:
no
Clinical signs:
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not specified
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Other effects:
not examined
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
Key result
Dose descriptor:
NOEL
Generation:
F1
Effect level:
225 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: overall effects
Key result
Critical effects observed:
no
Conclusions:
NO(A)EL = 225 ppm a.i.; Kathon™ 886 NAR has no adverse effects on the reproductive capability of male or female rats and no effect on fetal health or survival to day 21 at concentrations up to and including 225 ppm in the drinking water.
Executive summary:

OECD 415 one-generation reproduction study in rats with analytical confirmation of drinking water concentrations of Kathon™ 886. Kathon™ 886 NAR has no adverse effects on the reproductive capability of male or female rats and no effect on fetal health or survival to day 21 at concentrations up to and including 225 ppm in the drinking water. These values correspond to a dose level of 16.3 mg/kg/day in males and 24.7 mg/kg/day in females.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
22.7 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

C(M)IT/MIT was tested in two developmental toxicity studies in rats and in one study in rabbits.

Link to relevant study records

Referenceopen allclose all

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-11-03 till 1994-01-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: .
Qualifier:
according to guideline
Guideline:
EPA OPP 83-3 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
One non-pregnant female inadvertently sacrified on day 17 p.c. On day 10 p.c. 2 animals incorrectly dosed (dosage appr. 4 % higher).One female rat of the control group, which littered, had a body weight of 262 g due to pregnancy.
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
TEST ANIMALS
Sprague Dawley Crl: CD (SD)BR, from “specific pathogen free" colony
- Source: Charles River Wiga GmbH, 97633 Sulzfeld, Germany
following data only for females; males were not treated with the test article and were used for mating only
- Age at study initiation: : 8 to 12 weeks
- Weight at study initiation: 180 to 238 g
- Housing: individually in macrolon III-cages on autoclaved sawdust
- Diet (e.g. ad libitum): ad lib. Ssniff R10 standard diet
- Water (e.g. ad libitum): ad lib. tap water
- Acclimation period: 7 days prior to mating


ENVIRONMENTAL CONDITIONS
- Temperature (°C): (17) 19-25°C
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light):12/12

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: daily


VEHICLE

aqua bidestillata
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
first and last week of treatment; analysed by HPLC-UV;
result: analytical conc. =92-98% of nominal dose
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:4
- Length of cohabitation: during the night
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of gestation



Duration of treatment / exposure:
10 days, from day 6 - 15 post-coitum; 5 days postexposure-period;
Frequency of treatment:
daily for 10 consecutive days
Duration of test:
(23 d in total)
No. of animals per sex per dose:
25 inseminated females per group
Control animals:
yes, concurrent vehicle
Details on study design:
day 20 post-coitum: sacrificed
Maternal examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at least once daily

BODY WEIGHT: Yes
- Time schedule for examinations:Individually for days 0, 6, 9, 12, 16 and 20 post-coitum

FOOD CONSUMPTION: Yes Individually for the intervals from day 0-6, 6-9, 9-12, 12-16 and 16-20 post-coitum.

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: only macroscopically for changes

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 life/dead fetuses: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Intra-uterine deaths were classified as follows:
Early resorptions showed decidual or placental tissues only.
Late resorptions showed embryonic or fetal tissue in addition to placental tissue but did not include fetuses dying in utero within approximately 2 days prior to the terminal kill.
Dead fetuses included only the fetuses dying in utero within approximately the last 2 days.
The uteri of apparently non-pregnant females were immersed in a 10 per cent solution of ammonium sulphide to reveal evidence of implantation (Salewski technique).
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter
- Head examinations: No data
- Sex

Approximately half of the fetuses from each litter were eviscerated and the carcasses processed for skeletal examination (Alizarin staining technique).
The remaining half was fixed in ethanol and examined for visceral abnormalities using a modified Wilson-Barrow technique.
Dead fetuses were evaluated separately, if applicable. Structural deviations were classified as follows:
Malformation: rare and/or probably lethal, e.g. hydrocephaly.
Variation: changes which regularly occur also in control groups and which are not of functional significance.
In one litter each from group 2 (animal 45) and 4 (animal 94) all fetusses were determined for visceral examination were inadvertently eviscerated. Therefore only visceral examination of the heads was possible.
Statistics:
body weight, body weight change and food consumption: Levene's test for homogeneity of variances followed by rank transformation and the Levene's test in the case of heterogeneity only (p < 0.05, equivalent to 95 per cent confidence level) and ANOVA with Dunnett's two-tailed t-test to compare each treated group against the control group.
litter weight: the Bartlett's test for homogeneity of variance followed by rank transformation andBartlett's test in the case of heterogeneity only (p < 0.05, equivalent to 95 per cent confidence level) ;IF homogen: ANOVAwith Dunnett's two-tailed t-test was used to compare each treated group against the control group; IF heterogen Kruskal-Wallis test with Wilcoxon rank-sum test to compare each treated group against the control group.
number of corpora lutea, number of implantations, pre-implantation loss, total intra-uterine deaths, post-implantation loss, number of live fetuses and proportion of male fetuses: rank transformation followed by the Bartlett's test for homogeneity of variances. IF homogeneous: ANOVA, followed in the case of significant results (p < 0.05, equivalent to 95 per cent confidence level) by the Dunnett's two-tailed t-test to compare each treated group against the control group. IF heterogen: rank transformed data the Kruskal-Wallis test together with the Wilcoxon rank-sum test to compare each treated group against the control group.
mean fetal: rank transformation followed by the Bartlett's test for homogeneity of variances ANCOVA (covariate: number of fetuses). with Dunnett's two-tailed t-test was used to compare each treated group against the control group.
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
No mortalities were observed in this study.
CLINICAL OBSERVATIONS
Treatment-related clinical signs were observed in groups 3 (70 mg/kg) and 4 (139 mg/kg).
In group 3 (70 mg/kg), two animals showed gasping and/or wheezing respiration shortly after dosing an 1 or 2 days at the beginning of the treatment period. During the further course of treatment no compound-related clinical signs were observed.
In group 4 (139 mg/kg), six animals showed gasping and/or wheezing respiration shortly after dosing for 1 to 5 days. Mostly these signs were observed at the beginning of treatment but two animals showed them also during the second half of the treatment period.
In group 2 (28 mg/kg), no treatment-related clinical signs were observed.
BODY WEIGHT
Group mean body weight gain was slightly affected by treatment with Acticide 14 in groups 2 (28 mg/kg) and 3 (70 mg/kg), and moderately affected in group 4 (139 mg/kg).
In groups 2 (28 mg/kg) and 3 (70 mg/kg), mean body weight gain was slightly reduced from day 6 to 9 post-coitum. During the further course of treatment it was comparable to that in the control group. Evaluation for the entire treatment-period as well as for the entire study revealed a slight reduction of mean body weight gain in these groups.
In group 4 (139 mg/kg), mean body weight gain was moderately and statistically significantly reduced from day 6 to 9 post-coitum and slightly reduced from day 12 to 16 post-coitum. In consequence, mean body weight gain was also reduced from day 6 to 16 post-coitum and from day 0 to 20 post-coitum.
FOOD CONSUMPTION
A minimal to slight effect of treatment with Acticide 14 an mean daily food consumption was observed in all dose groups.
In groups 2 (28 mg/kg) and 3 (70 mg/kg), mean daily food consumption was minimally lower than the control group from day 6 to 9 post-coitum, which is considered to be treatment related. During the further course of the study food consumption in these groups was comparable to that in the control group.
In group 4 (139 mg/kg), mean daily food consumption was slightly reduced from day 6 to 9 post-coitum and slightly and statistically significantly reduced from day 12 to 16 post-coitum. Consequently, evaluation for the entire treatment-period as well as the entire study revealed a slight reduction of food consumption in this group.
NECROPSY FINDINGS
Necropsy did not reveal any treatment-related findings. In one animal each from group 3 (70 mg/kg) and 4 (139 mg/kg) findings in the kidneys and/or liver were detected. These single observations are considered to be incidental and not attributable to treatment with Acticide 14.
Dose descriptor:
LOAEL
Effect level:
28 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
IMPLANTATION
No effect of treatment with Acticide 14 on implantation data was observed. The pre-implantation loss was comparable and within the normal range in all groups.
POST-IMPLANTATION LOSS
The post-implantation loss was not affected by treatment with Acticide 14. The observed inter-group differences are considered to be incidental.
NUMBER, SEX AND WEICHT OF THE FETUSES
No effect of treatment with Acticide 14 was observed on number, sex and weight of the fetuses.
The mean number of fetuses per litter was comparable in all groups.
The fetal sex distribution in the dose groups was comparable to that in the control group.
The mean fetal weight was similar in all groups.
FETAL DEFECTS
Fetal examination did not reveal any treatment-related malformations or variations. External, visceral and skeletal malformations were found in all groups including the control group.
In group 2 (28 mg/kg), two malformed fetuses were found in two different litters. In one fetus a single common ventricle of the heart was detected at visceral examination. The second fetus showed skeletally absent rib(s).
In group 3 (70 mg/kg), three fetuses with malformations were detected in three different litters. In two fetuses malformations such as asplenia or anorchism were detected at visceral examination. Externally, the third fetus showed microtia and anasarca. Visceral examination of this fetus did not reveal any further findings.
In group 4 (139 mg/kg), two malformed fetuses were found in two different litters. One fetus showed microsplenia at visceral examination. Externally, the second fetus showed agnathia. Visceral examination of this fetus revealed malformations such as anophthtalmia, aglossia and nares non-patent.
One control fetus showed anal atresia as an external malformation.
Visceral or skeletal variations were detected in fetuses of all study groups.
The type and the incidence of the observed malformations and variations did not show a dose-relationship and did not indicate any effect of treatment with Acticide 14.
Dose descriptor:
NOAEL
Effect level:
>= 19.6 mg/kg bw/day
Basis for effect level:
other: embryotoxicity
Dose descriptor:
NOAEL
Effect level:
>= 19.6 mg/kg bw/day
Basis for effect level:
other: teratogenicity
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
Administration of Acticide 14 to pregnant rats during the phase of organogenesis did not result to observation of any signs of teratogenicity or embryotoxicity.
Executive summary:

The potential of a 14% aqueous solution of 3 parts 5 -chloro- 2 -methyl-2H-isothiazol-3 -one and 1 part 2 -methyl-2H-isothiazol-3 -one (cited as Acticide 14 in the report) to induce teratogenic effects in rats was evaluated in a study according to guideline EPA OPP 83 -3. Pregnant female Sprague-Dawley rats were treated with the test substance by oral gavage during the period of organogenesis (days 6 -15 post coitum). Animals were observed for mortality, signs of toxicity, food consumption and body weight gain during the treatment and a post-exposure period of 5 days. At day 20 of gestation, animals were sacrificed and examined for macroscopic pathological abnormalities. Uterine contents were examined for signs abnormal pregnancy courses, and fetuses were examined for external, visceral and skelettal abnormalities.

Treatment with the test article resulted in maternal toxicity with clearly distingished dose-dependent grades of severity (clinical signs, moderately reduced body weight gain, slightly reduced food consumption). In spite of the observed adverse maternal effects, treatment with the test article did not have any influence on the embryonic and fetal development, as there was no embryotoxicity and no teratogenicity detected in any of the dose groups.

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Rohm and Haas, Batch No. 78/4435

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Soluble and stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dilution in water
- Final dilution of a dissolved solid, stock liquid or gel: 10, 30, 100 ppm a.i.

OTHER SPECIFICS: Purity of test material was 15%
Species:
rat
Strain:
other: Sprague-Dawley CR
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Massachusetts, USA
- Age at study initiation: Not described
- Weight at study initiation: Males ranged from 300 to 350 g and females ranged from 180 to 200 g
- Fasting period before study: Not described
- Housing: Not described
- Diet (e.g. ad libitum): Not described
- Water (e.g. ad libitum): Not described
- Acclimation period: Not described
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Prepared fresh each day of dosing
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- Length of cohabitation: Up to 3 weeks
Duration of treatment / exposure:
Day 6-15 post mating
Duration of test:
Females were killed on day 20 of gestation
Dose / conc.:
10 ppm
Remarks:
Nominal a.i. in water
Dose / conc.:
30 ppm
Remarks:
Nominal a.i. in water
Dose / conc.:
100 ppm
Remarks:
Nominal a.i. in water
No. of animals per sex per dose:
25 females
Control animals:
yes, concurrent vehicle
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations checked in the table were included

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Day 0, 6, 11, 15, and 20 of gestation

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: Uterus and ovaries
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: No
- Number of late resorptions: No
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: two-thirds per litter
- Skeletal examinations: Yes: two-thirds per litter
- Head examinations: No data
Statistics:
Not described
Indices:
n/a
Historical control data:
Not described
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Wheezing
Dermal irritation (if dermal study):
not examined
Mortality:
mortality observed, treatment-related
Description (incidence):
Six maternal deaths occurred in the treated groups; 1 at 10 mg/kg, 2 at 30 mg/kg and 3 at 100 mg/kg.
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
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
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Changes in number of pregnant:
no effects observed
Other effects:
not examined
Key result
Dose descriptor:
NOAEL
Effect level:
15 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Remarks on result:
not determinable due to absence of adverse toxic effects
Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): 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:
not examined
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
not examined
Key result
Dose descriptor:
NOAEL
Effect level:
15 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Conclusions:
Kathon™ 886 is non-teratogenic to the rat when administered at dosages of 100 mg/kg/day (15 mg ai/kg bw/day) during organogenesis.
Executive summary:

The study was initiated prior to the adoption of teratogenicity study guidelines. However, the principles of OECD Guideline 414 were followed. Kathon™ 886 is non-teratogenic to the rat when administered at dosages of 100 mg/kg/day (15 mg ai/kg bw/day) during organogenesis.

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 83-3 (Prenatal Developmental Toxicity Study)
Deviations:
no
GLP compliance:
yes
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Rohm and Haas, Batch No. 32092

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Soluble and stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dilution in water

OTHER SPECIFICS: Purity of test material was 13.4%
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Animals, Denver, Pennsylvania, USA
- Age at study initiation: Sexually mature and 5 ½ to 6 months old
- Weight at study initiation: 2.6 to 4.1 kg on Day 0 of gestation
- Fasting period before study: Not described
- Housing: Not described
- Diet (e.g. ad libitum): Not described
- Water (e.g. ad libitum): Not described
- Acclimation period: Not described
Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Impregnation procedure: cohoused
Duration of treatment / exposure:
Day 7-19 of gestation
Frequency of treatment:
Daily
Duration of test:
Day 29 of gestation
Dose / conc.:
0.5 mg/kg bw/day (actual dose received)
Remarks:
Based on a.i.
Dose / conc.:
2 mg/kg bw/day (actual dose received)
Remarks:
Based on a.i.
Dose / conc.:
8 mg/kg bw/day (actual dose received)
Remarks:
Based on a.i.
Dose / conc.:
20 mg/kg bw/day (actual dose received)
Remarks:
Based on a.i.
No. of animals per sex per dose:
16 females
Control animals:
yes, concurrent vehicle
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily between days 7-19 G and once per day on days 2-6 G and days 20-29 G.
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice daily between days 7-19 G and once per day on days 2-6 G and days 20-29 G.

BODY WEIGHT: Yes
- Time schedule for examinations: 0, 7, 9, 11, 14, 17, 20, 29 days of gestation

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
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
Fetal examinations:
- External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No data
Statistics:
Not described
Indices:
Not described
Historical control data:
Not described
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
A treatment-related increase in clinical signs (scant faeces, no faeces, and diarrhea) were noted at 8 and 20 mg a.i./kg.
Dermal irritation (if dermal study):
not examined
Mortality:
mortality observed, non-treatment-related
Description (incidence):
No treatment-related deaths at 0, 0.5, 2 or 8 mg a.i./kg. At 20 mg a.i./kg, 15/16 animals were sacrificed moribund on or before day 15 G.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Treatment-related decrease in body weight gain at 8 mg a.i./kg
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Treatment-related decrease in feed consumption at 8 mg a.i./kg
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Gross post-mortem changes (thickened stomach, reddened stomach, and necrotic stomach) were seen at 20 mg a.i./kg but no at lower doses
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
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
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Changes in number of pregnant:
no effects observed
Other effects:
not examined
Key result
Dose descriptor:
NOEL
Effect level:
2 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
body weight and weight gain
mortality
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): 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 examined
Key result
Dose descriptor:
NOEL
Effect level:
8 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no

Table A6.8.1.b/01-1. Table for Teratogenic effects

Maternal effects

Parameter

Controldata

Low dose (0.5 mg as/kg)

Medium dose (2 mg as/kg)

Medium-high dose                (8 mg as/kg)

High dose  (20 mg as/kg)

Number of dams examined

16

16

16

16

16

Clinical findings during application of test substance

none

none

none

inc.

inc.

Mortality of dams

state %

0/16

0/16

0/16

1/16

 16/16

Body weight

none

none

none

dec.

---

Food consumption

none

none

none

dec.

---

Post-mortem gross changes to stomach

none

none

none

none

inc.

--- no data due to early death, dec.: decrease, inc.: increase.

Conclusions:
No treatment related increases were detected in the type or incidence of external, visceral or skeletal malformations, variations due to retarded development or in the total of these two categories combined. Based on the results of this study, Kathon™ 886 MW Biocide when administered orally by gavage to pregnant rabbits has a maternal no observable effect level (NOEL) of 2 mg a.i./kg and an embryo-fetal NOEL of 8 mg a.i./kg.
Executive summary:

OECD Guideline 414, US EPA OPP 83-3 study. No treatment-related deaths at 0, 0.5, 2 or 8 mg a.i./kg. At 20 mg a.i./kg, 16/16 animals were sacrificed moribund on or before day 15 G. Based on the results of this study, Kathon™ 886 MW Biocide when administered orally by gavage to pregnant rabbits has a maternal no observable effect level (NOEL) of 2 mg a.i./kg and an embryo-fetal NOEL of 8 mg a.i./kg. No treatment related increases were detected in the type or incidence of external, visceral or skeletal malformations, variations due to retarded development or in the total of these two categories combined.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

CMIT/MIT carries a mandatory classification in accordance with Annex VI Regulation EC 1272/2008 and is not classified for reprodevelopmental effects.

Additional information