2-methylpentane-1,5-diamine

Endpoint summary

Description of key information

Oral
In a reliable study similar to OECD guideline 401 (Klimisch 2), MPMD was administered via oral gavage to 10 male CD rats per dose group. The LD50 value was calculated to be 1690 mg/kg bw. Clinical signs included salivation, lung noise, diarrhea and stained perineum.

Inhalation
In a reliable study (Klimisch 2) male and female rats were subjected to a 1 hour inhalation exposure to aerosol/vapour mixture with various MPMD concentrations. Clinical signs of toxicity could be found in all dose groups in different severity. Mortality was observed once during the exposure and more often within the 14 day observation period. Under the conditions of this test, the one-hour LC50 of the test material was 4.9 mg/L for male and female rats (95% CI 3.1 to 7.2 mg/L).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 MAR 1984 to 09 APR 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines/standards

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no necroscopy performed, no data produced for the other sex (females)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Crl:CD rats

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, New York, USA
- Age at study initiation: 7 weeks
- Weight at study initiation: mean boda weight per dosimg group: 237-238 g
- Fasting period before study: no data
- Housing: single
- Diet: Purina Certified Rodent Chow #5002, ad libitum
- Water: ad libitum
- Acclimation period: 1 week

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100, 150, 200 300 mg/ml, depending on the dose
- Amount of vehicle (if gavage): between 2.06 and 2.69 ml depending on the dose
- Purity: distilled water

MAXIMUM DOSE VOLUME APPLIED: 2.69 ml

Doses:

1000, 1300, 1700, 2000, 3000 mg/kg bw, one single application

No. of animals per sex per dose:

10 male rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily until signs of toxicity subsided, and then at least every other day
- Necropsy of survivors performed: no

Statistics:

The LD50 was calculated with a 95 % confidence interval.

Sex:

male

Dose descriptor:

LD50

Effect level:

1 690 mg/kg bw

Based on:

test mat.

95% CL:

1 490 - 1 930

Remarks on result:

other: details see below

Mortality:

Deaths occurred within 8 days after dosing
1000 mg/kg: 0/10
1300 mg/kg: 2/10
1700 mg/kg: 4/10
2000 mg/kg: 8/10
3000 mg/kg: 10/10

Clinical signs:

other: other: non lethal dose: salivation, lung noise, diarrhea, stained perineum lethal dose: shortly after dosing, blood was observed in the urine of rats dosed at 1700 mg/kg and above; this was not seen 24 h after dosing. Predominant clinical signs included

Gross pathology:

not performed

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the applied test condition the test substance has an LD50 value of 1690 mg/kg bw.

Executive summary:

In a study similar to OECD guideline 401, test substance was administered via oral gavage to 10 male CD rats per dose group (1000, 1300, 1700, 2000, 3000 mg/kg bw). The LD 50 value was calculated to be 1690 mg/kg bw. Clinical signs included salivation, lung noise, diarrhea and stained perineum.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 690 mg/kg bw

Quality of whole database:

The study is reliable (Klimisch 2), similar to OECD TG 401 and therefore of good quality.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 28 DEC 1987 to 14 JAN 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication/study report which meets basic scientific principles

Qualifier:

according to guideline

Guideline:

other: International Maritime Dangerous Goods (IMDG) Protocol to determine packaging classification

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

only 1 hour exposure

GLP compliance:

yes

Remarks:

according to EPA GLP Regulations (40 CFR 160)

Test type:

acute toxic class method

Limit test:

no

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 Breeding Laboratories, Kingston, New York, USA
- Age at study initiation: young adults
- Housing: during test rats were housed éither individually or in pairs (sexes separate) in stainless steel wire-mesh cages
- Diet: Purina certified Rodent Chow #5002; ad libitum (except during exposure)
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2
- Humidity (%): 50 +/- 10
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

other: inhalation of a aerosol/vapour mixture

Type of inhalation exposure:

nose only

Vehicle:

other: air and nitrogen

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical glass chamber
- Exposure chamber volume: 38 liter
- Method of holding animals in test chamber: restraining
- System of generating particulates/aerosols: Atmospheres of test material were generated by pumping the liquid test material into an Instatherm Flask heated to 187-228°C. The liquid was metered with a Harvards Model 975 Compact Infusion Pump. Nitrogen introduced at the flask swept the vapours of test material into a glass transfer tube. Dilution air was added in the transfer tube where an aerosol/vapour mixture was formed. The vapour/aerosol mixture then discharged directly into a 38-liter cylindrical glass exposure chamber and was dispersed with a baffle to promote uniform chamber distribution.
In order to attain a higher chamber concentration in the last exposure, 2 syringes and 2 Instatherm flasks were used to increase the vapourisation capacity. Chamber concentratiens of test material were controlled by varying the test material feed rates into the flask.
- Method of particle size determination:Sierra Series 210 Cascade Impactor
- Treatment of exhaust air: Chamber atmospheres were exhausted through a dry-ice cold trap, and a MSA cartridge filter prior to discharge into a fume hood.
- Temperature and humidity in chamber: 23 to 25 °C; 28 to 70% relative humidity

TEST ATMOSPHERE
- Brief description of analytical method used: The atmospheric concentration of test material was monitored at approximately 15-minute intervals during each exposure. Known volumes of chamber atmosphere were drawn through two tandem glass midget impingers which contained methanol as a trapping solvent. Impinger samples were analysed in duplicate with a Hewlett-Packard 5730A gas chromatograph equlpped with a Flame ionization detector. Samples were chromatographed isothermally at 110°C on a 5 m x 0.53 mm fused silica megabore column coated (1.2 um film thickness) with methyl silicone gum. The atmospheric concentration of test material was determined by comparing the detector response of samples with standard curves. Standards were prepared prior
to each exposure by quantitatively diluting the test material in methanol.
Aerodynamic particle size (mass median aerodynamic diameter and percent particles less than 10 um diameter) was determined with a Sierra Series 210 cascade impactor during each exposure.
Chamber temperature was measured with a mercury thermometer, oxygen concentration was measured with a Biosystems Model 3100R oxygen monitor, and relative humidity was measured with a Bendix Model 566 psychrometer.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

1 h

Concentrations:

0.37, 1.7, 2.5, 6.6, and 10 mg/l

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: daily for the first 7 days after exposure and daily except on weekends during the second 7 days after exposure
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Statistics:

The program used calculates the LC50 according to the probit analysis of Finney (1971; Finney, DJ; Probit ANalysis, 3rd Edition, Cambridge University Press). For the data in question a probit model on non-transformed dose data gave the best fit, as judged by the Pearson or likelihood-ratio chi-squared tests, and tighter fiducial limits. It is further the judgement of the statistician, that a probit model on the non-transformed dose data is the proper choice for this data.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4.9 mg/L air (analytical)

Based on:

test mat.

Remarks:

(aerosol)

95% CL:

3.1 - 7.2

Exp. duration:

1 h

Mortality:

for details see "Any other information on results incl. tables"

Clinical signs:

other: for details see "Any other information on results incl. tables"

Exposure conditions and mortality

Conc. [mg/L] Mean (SD; range) (a)	Particle size - MMD [micrometre] (b)	Particle size - [%] < 10 micrometres (c)	Mortality (#deaths/#exposed) Males ; Females
0.37 (0.22; 0.068 to 0.53)	3.4	95	1/5 ; 0/5
1.7 (0.41; 1.3 to 2.2)	4.2	89	3/5 ; 1/5
2.5 (0.63; 1.8 to 3.4)	3.8	84	1/5 ; 2/5
6.6 (1.2; 6.2 to 8.1)	3.8	90	2/5 ; 2/5
10 (0.74; 9.5 to 11)	3.1	94	5/5 ; 5/5
a. values shown represent the mean, standard deviation (S.D.) and range based on 4 samples taken during exposure.     b. Mass median aerodynamic diameter c. Percent by weight of particles with aerodynamic diameter less than 10 micrometres.

Two male rats and one female rat in the 10 mg/L exposure group died during exposure. All other rats in this group died within 48 hours of exposure. Deaths occurred at lower exposure concentrations at various times during the 14-day recovery period (deaths occurred on recovery days 1, 2, 3, 4, 7, 10, 12, and 14). There was no clear dose-related trend seen with respect to when the deaths occurred.

During exposure, rats in the 1.7 and 2.5 mg/L exposure groups showed red nasal discharge. In addition, rats in the 2.5 mg/L group showed a decreased response to sound. Rats in the 6.6 and 10 mg/L groups could not be seen during exposure, therefore it was not possible to note clinical signs during exposure. Immediately after being released from their restrainers, rats in the 0.37 and 1.7 mg/L exposure groups showed red nasal and ocular discharges, a clinical sign that is common for rats under restraint. Upon release from their restrainers, rats that were exposed to concentrations of 2.5 mg/L and higher showed red ocular, nasal, or oral discharges, labored breathing, and gasping. In addition, rats in the 10 mg/L exposure group showed hunched posture.

During the 14-day recovery period, the only clinical sign of toxicity observed in the rats exposed to 0.37 mg/L was slight to severe weight loss ("slight" corresponds to < 10 grams; "Moderate" corresponds to 10 to 20 grams; "severe" corresponds to >20 gram), which occurred over one to three days. Numerous clinical signs of toxicity were observed in both male and female rats exposed to 1.7 mg/L and higher concentrations, but there was no clear dose-response trend seen among these exposure groups. Common clinical signs observed in rats exposed to higher concentrations included slight to severe weight loss, red-ocular, -nasal, or -oral discharge; wet urine- or feces-stained perineum, diarrhea, high carriage, hunched posture, lung noise, labored breathing, and gasping.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In this study male and female rats were subjected to a one hour inhalation exposure to an aerosol/vapour mixture with various test material concentrations. Clinical signs of toxicity could be found in all dose groups in different severity. Mortality was observed once during the exposure and within the 14 day observation period. The resulting LC value for male and female animals was 4.9 mg/L after one hour exposure.

Executive summary:

Five groups of 5 male and 5 female Crl:CD*BR rats were exposed, nose-only, to atmospheres of test material for a single, one-hour period. Mixed aerosol/vapour test atmospheres were generated by vaporising the liquid and were characterised by gas chromatography and particle size analysis. After exposure, rats were weighed and observed for clinical signs of toxicity during a 14-day recovery period. Under the conditions of this test, the one-hour LC50 of the test material was 4.9 mg/L for male and female rats (95% confidence limits of 3.1 and 7.2 mg/L).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

4.9 mg/L air

Physical form:

inhalation: mixture of vapour and aerosol / mist

Quality of whole database:

The study is reliable (Klimisch 2), similar to OECD TG 403 and therefore of good quality.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No systemic toxic effects were observed after acute oral or inhalative exposure indicative of a specific target organ toxicity (remark: red nasal and ocular discharges after inhalational exposure was not used as effect leading to STOT classification, because it is a clinical sign that is common for rats under restraint. However apart from rather systemic effects only local irritating effects were observed after repeated inhalation exposure to the substance (see respective section for further details) and the local effects observed are clearly due to the corrosivity of the substance. Based on this fact the classification STOT – single exposure category 3 is proposed.

 

Acute toxicity: inhalation

Considering acute toxicity after inhalation exposure there is one reliable study for MPMD which can be used for classification. The LC50 value estimated after 1 hour aerosol/vapour exposure was 4.9 mg/L for male and female rats. According to Regulation (EC) No 1272/2008 Annex I section 3.1.2.1.c this value has to be divided by 4 in order to receive a proper value for classification purposes. Thus, in the end a LC50 value of 1.23 mg/L has to be used for classification.

 

Acute toxicity: dermal

The substance is corrosive to skin and according to REACH Annex VII, No. 8.5, Column 2 no acute toxicity test by dermal route has to be performed if the substance is classified as corrosive to skin.

Justification for classification or non-classification

Based on the LD50 and LC50 values presented above, this substance has to be classified for acute oral and inhalative toxicity according to Regulation (EC) No 1272/2008 (i. e. category 4 for each route of exposure). Furthermore, the substance is going to be classified for specific target organ toxicity – single exposure category 3 according to Regulation (EC) No 1272/2008.