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Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Crjh : CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan Inc.
- Age at study initiation: no data
- Weight at study initiation: males 115 - 166 g, females 102 - 127 g
- Fasting period before study: yes
- Housing: 5 per cage in polycarbonate cages
- Diet (e.g. ad libitum): pelletized rat diet (rat.MF, Oriental Yeast Co.), ad libitum
- Water (e.g. ad libitum): tap water through polycarbonate bottles, ad libitum
- Acclimation period: more than a week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- Humidity (%): 50 - 60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.18 - 0.7 mL TS/mL olive oil according to dose
- Amount of vehicle (if gavage): 1 mL/100 g bw
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 1 mL/100 g bw
Doses:
males: 1.73, 2.21, 2.78, 3.46, 4.32, 5.38, and 6.72 g/kg bw (1.8, 2.3, 2.9, 3.6, 4.5, 5.6, 7.0 mL/kg)
females: 2.78, 3.46, 4.32, 5.38, 6.72 (2.9, 3.6, 4.5, 5.6, 7.0 mL/kg)
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: several times at day of administration, once or more times daily thereafter until 14 days
(time of sacrifice). Body weights were measured shortly before, 7 and 14 days after administration.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
LD50 values were determined using the method of Litchfield and Wilcoxon.
Sex:
male
Dose descriptor:
LD50
Effect level:
4 130 mg/kg bw
95% CL:
3 550 - 4 800
Remarks on result:
other: LD50 is reported as 4.3 mL/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
4 320 mg/kg bw
95% CL:
3 650 - 5 090
Remarks on result:
other: LD50 is reported as 4.5 mL/kg bw
Mortality:
1.58 g/kg group:  0/10
2.20 g/kg group: 1/10 (day 2)
2.78 g/kg group:   1/20 (day 3)
3.46 g/kg group:   6/20 (days 2-4)
4.32 g/kg group:  11/20 (days 1-5)
5.38 g/kg group:  14/20 (days 1-5)
6.72 g/kg group:  20/20 (days 1-6)
Clinical signs:
Reduced activity, reduced muscle tonus, toe walking, diarrhea, incontinence, haemic nasal discharge, emaciation
Body weight:
Compared to the day of treatment (start of the experiment), the body weights measured were increased at day 7 and further increased at day 14.
Gross pathology:
Dead animals
Dose-related discolored liver, discolored and atrophic spleen and kidneys, reddish purple appearance of the adrenal glands, hypertrophy of the adrenal glands, scattered reddish spots in and reddish appearance of the lungs, hemorrhage in the thymus gland
Surviving animals
Occasionally in male, but not in female animals, scattered reddish spots in the lung, atrophy of spleen and hypertrophy of mesentery lymph nodes.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a valid acute oral toxicity study according to OECD test guideline 401, LD50 values of 4130 and 4320 mg/kg bw were determined for male and female rats respectively.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
4 130 mg/kg bw
Quality of whole database:
acceptable for assessment, SAR

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted 1981
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, Fuellinsdorf, Switzerland
- Age at study initiation: males 11 weeks, females 13 weeks
- Weight at study initiation: males 237.5 - 255.6 g, females 218.3 - 239.7 g
- Housing: 5 per cage in makrolon cages, type IV, with standard softwood bedding
- Diet (e.g. ad libitum): pelleted standard Kliba 343 rat maintenance diet (Klingenthalmuehle AG. Kaiseraugst, Switzerland), ad libitum
- Water (e.g. ad libitum): community tap water from Geneva, ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 09.11.1987 To: 01.12.1987
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: exposure chamber according to Sachsse et al (1973, 1976): Breathing atmosphere (aerosol) is passed through a central
cylindrical tube vertically positioned to which animal confinement chambers are radially attached. From the internal active exposure chamber,
small tubes lead to the breathing zone of the attached confinement chambers. Surplus breathing air and exhaled air are discharged through
an outer cylindrical tube positioned around the internal active chamber.
- Exposure chamber volume: volume of the internal active chamber: 1 L
- Method of holding animals in test chamber: Macrolon restraint tubes of suitable size and shape vertically attached to the exposure chamber
- System of generating particulates/aerosols: The test atmosphere was generated by a constant volume reservoir feeding a Hospitak No. 950
nebulizer following dissolution with water. Following the nebulizer, a dilution system was used to dilute the test article output of the nebulizer
with clean air to the concentration required for the study. The aerosol generating system was designed to create an aerosol with a mass median
diameter of 3 µm or less. Following aerosolization, the test article was discharged into the exposure chamber.
- Method of particle size determination: separation of particles using a Mercer 7 stage cascade impactor. The sampling air flow was 1.0 L/min
and the mass content of the different stages of the impactor was assessed gravimetrically.
- Temperature, humidity, pressure in air chamber: 21°C, 12% (relative humidity), slight positive pressure in inner chamber and slight negative
pressure in outer chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: Test substance was sampled by passing test atmosphere through three in line gas washing bottles
containing ice-cold acetonitrile as solvent. Aliquots of this solution were analyzed by HPLC (solvent acetonitrile/water 70/30, column RP-18).
KMC was used as external standard for calibration (see Appendix D).
- Samples taken from breathing zone: yes

VEHICLE
- no

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 36.3% ≤4.6 and >3.0 µm, 23.3% ≤3.0 and >2.13 µm, 40.4% ≤2.13 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): no data
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see above
Duration of exposure:
4 h
Concentrations:
5.64 mg/l (Limit test; mean analytical exposure concentration)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once per hour during exposure, once after exposure on test day 1 and twice daily thereafter,
body weight measurements at days 1 (day of exposure), 8, and 15 of test
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight; lungs from all animals were collected at necropsy and
fixed in a neutral phosphate buffered 4% formaldehyde solution.
Statistics:
No statistics
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.64 mg/L air
Based on:
test mat.
Remarks:
(aerosol)
Exp. duration:
4 h
Mortality:
2/5 females died at day 14 post exposure; no deaths among males.
Clinical signs:
During exposure: slight to moderate nose bleeding (epistaxis), no other significant signs.
After exposure: slight to moderate signs of discomfort and physiological distress: hunched posture, piloerection, distended abdomen, tremor, impaired breathing, salivation and rhinorrhea. Impaired breething and piloerection continued until the end of the observation period. Rales were observed starting at day 2 and continued into week 2 of observation.
Symptoms were more pronounced in females than in males.
Body weight:
Males: Mean body weight decreased from test day 1 to day 8. Until test day 15, mean body weight increased again,
but the starting value was not reached.
Females: Mean body weight decreased continuously over day 8 up to day 15 (only 3 animals at day 15).
Gross pathology:
red spots in the lung
Conclusions:
In an acute inhalation toxicity test using only one concentration (5.64 mg/L, limit test), 5 rats/sex were exposed to KCM (diisopropylnaphthalene) as aerosol for 4 hours.Two of the female rats died at day 14 (mortality 2/10 total). The LC50 for acute inhalation toxicity can be assessed to be >5.64 mg/L based on the mortality observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
5 640 mg/m³
Quality of whole database:
acceptable for assessment, SAR

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: four to seven weeks
- Weight at study initiation: males 245 - 255 g, females 205 - 225 g
- Fasting period before study: no data
- Housing: singly in Makrolon-cages with bedding
- Diet (e.g. ad libitum): R 4 complete rat diet (Ssniff Versuchstier-Diäten GmbH, Soest, Germany), ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23
- Humidity (%): 40 - 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 /12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: ca 34 cm²
- % coverage: ca. 10% of body surface
- Type of wrap if used: occlusive wrap (Leukoplast)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance residues were washed off with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4500 mg/kg
- Concentration (if solution): pure test substance
Duration of exposure:
24 hours
Doses:
4500 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: 0.25, 0.5, 1, 2, and 4 hours after TS administration, daily thereafter;
weighing: at days -1, 0 (day of administration), 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
no calculations
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 500 mg/kg bw
Remarks on result:
other: only one dose administered (limit test); no mortality
Mortality:
No mortality
Clinical signs:
No clinical signs
Gross pathology:
No macroscopic findings
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity test using only one dose (4500 mg/kg bw, limit test), 5 rats/sex were exposed to KMC 113/1 (diisopropylnaphthalene) for 24 hours. No mortality and no clinical or gross pathological findings were observed. The LD50 for acute dermal toxicity can be assessed to be >4500 mg/kg bw under the conditions of this test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
4 500 mg/kg bw
Quality of whole database:
acceptable for assessment, SAR

Additional information

Justification for classification or non-classification

The assessment of acute toxicity has been based on read-across to closely structure-related substances, such as methylnaphthalene and diisopropylnaphthalene (DIPN). It is assumed that MIPN isomer mixture (MIPN) shows a similar acute toxicity profile. Hence, no classification is required for the target compound, as LD/LC50 values are above classification limits of Regulation (EC) No 1272/2008.